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However, many studies are still needed in order to mimic the physiological environment with 3D cell-growth systems. The mechano-physical properties of the microenvironment are relevant for the invasiveness of cancer cells and for their drug resistance. In this study, 3D tumoroids of human oral squamous cell carcinoma (OSCC) CAL27 cells of different stiffnesses were produced using a tunable PEG\u2013silk fibroin hydrogel (PSF), and the antitumor activity of the peptide CIGB300, an anticancer therapeutic peptide, with respect to these 3D tumoroid models was assessed. Furthermore, spectroscopic studies on the CIGB300 peptide are reported regarding its structure, stability, aggregation and diffusion properties. For the first time, the diffusion of the peptide CIGB300 in tunable silk fibroin hydrogels of different stiffnesses is investigated over time via fluorescence spectroscopy as a potential tool in drug-screening using hydrogel-based 3D tumoroids.<\/jats:p>","DOI":"10.3390\/ijms27041973","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:51:09Z","timestamp":1771491069000},"page":"1973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Microenvironment Rheology Modulates the Effect of the Anticancer Peptide CIGB300 on 3D Head and Neck Tumoroids"],"prefix":"10.3390","volume":"27","author":[{"given":"Silvia","family":"Buonvino","sequence":"first","affiliation":[{"name":"Departmental Faculty of Medicine, UniCamillus-Saint Camillus International University of Health and Medical Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Paduano","sequence":"additional","affiliation":[{"name":"Department of Chemical Science and Technologies, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0516-5683","authenticated-orcid":false,"given":"Valeria","family":"Stefanizzi","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilda","family":"Garay","sequence":"additional","affiliation":[{"name":"Peptide Synthesis Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 10600, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5791-604X","authenticated-orcid":false,"given":"Silvio","family":"Perea","sequence":"additional","affiliation":[{"name":"Department of Pharmaceuticals, Center for Genetic Engineering and Biotechnology (CIGB), 31 Ave., Playa, Havana 10600, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0878-1799","authenticated-orcid":false,"given":"Beatrice","family":"Macchi","sequence":"additional","affiliation":[{"name":"Department of Chemical Science and Technologies, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-7441","authenticated-orcid":false,"given":"Mariano","family":"Venanzi","sequence":"additional","affiliation":[{"name":"Department of Chemical Science and Technologies, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"NAST Center (Nanoscience and Nanotechnology and Innovative Instrumentation), University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7694-5279","authenticated-orcid":false,"given":"Sonia","family":"Melino","sequence":"additional","affiliation":[{"name":"NAST Center (Nanoscience and Nanotechnology and Innovative Instrumentation), University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Department of Experimental Medicine, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.semradonc.2004.04.008","article-title":"Tumor Microenvironmental Physiology and Its Implications for Radiation Oncology","volume":"14","author":"Vaupel","year":"2004","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Law, A.M.K., Rodriguez de la Fuente, L., Grundy, T.J., Fang, G., Valdes-Mora, F., and Gallego-Ortega, D. (2021). Advancements in 3D Cell Culture Systems for Personalizing Anti-Cancer Therapies. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.782766"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1002\/mog2.62","article-title":"Cancer Stem Cells: Signaling Pathways and Therapeutic Targeting","volume":"2","author":"Talukdar","year":"2023","journal-title":"MedComm\u2014Oncology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100862","DOI":"10.1016\/j.mtbio.2023.100862","article-title":"Modelling the Disease: H2S-Sensitivity and Drug-Resistance of Triple Negative Breast Cancer Cells Can Be Modulated by Embedding in Isotropic Micro-Environment","volume":"23","author":"Buonvino","year":"2023","journal-title":"Mater. Today Bio"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2400040","DOI":"10.1002\/adhm.202400040","article-title":"3D Cell Migration Chip (3DCM-Chip): A New Tool toward the Modeling of 3D Cellular Complex Systems","volume":"13","author":"Buonvino","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1177\/1087057106292763","article-title":"Rapid Generation of Single-Tumor Spheroids for High-Throughput Cell Function and Toxicity Analysis","volume":"11","author":"Ivascu","year":"2006","journal-title":"SLAS Discov."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5110","DOI":"10.1364\/AO.46.005110","article-title":"Estimating the Cell Density and Invasive Radius of Three-Dimensional Glioblastoma Tumor Spheroids Grown In Vitro","volume":"46","author":"Stein","year":"2007","journal-title":"Appl. Opt."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/j.drudis.2016.06.024","article-title":"Cell Spheroids: The New Frontiers in In Vitro Models for Cancer Drug Validation","volume":"21","author":"Chatzinikolaidou","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Buonvino, S., Ciocci, M., Seliktar, D., and Melino, S. (2021). Photo-Polymerization Damage Protection by Hydrogen Sulfide Donors for 3D-Cell Culture Systems Optimization. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116095"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/BF00689632","article-title":"Drug and Radiation Resistance in Spheroids: Cell Contact and Kinetics","volume":"13","author":"Olive","year":"1994","journal-title":"Cancer Metastasis Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1093\/jnci\/djm135","article-title":"Drug Resistance and the Solid Tumor Microenvironment","volume":"99","author":"Galmarini","year":"2007","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.yexcr.2014.01.017","article-title":"3D High-Content Screening for the Identification of Compounds That Target Cells in Dormant Tumor Spheroid Regions","volume":"323","author":"Wenzel","year":"2014","journal-title":"Exp. Cell Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"20131124","DOI":"10.1098\/rsif.2013.1124","article-title":"A Method for Estimating the Oxygen Consumption Rate in Multicellular Tumour Spheroids","volume":"11","author":"Grimes","year":"2014","journal-title":"J. R. Soc. Interface"},{"key":"ref_14","unstructured":"CIGB Centro de Ingenier\u00eda Gen\u00e9tica y Biotecnolog\u00eda (2025, December 10). Available online: https:\/\/www.cigb.edu.cu\/en\/project\/cigb-300-lung\/."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s11010-008-9814-5","article-title":"CIGB-300, a Novel Proapoptotic Peptide That Impairs the CK2 Phosphorylation and Exhibits Anticancer Properties Both In Vitro and In Vivo","volume":"316","author":"Perea","year":"2008","journal-title":"Mol. Cell. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1053\/j.seminoncol.2018.04.006","article-title":"CIGB-300: A Peptide-Based Drug That Impairs the Protein Kinase CK2-Mediated Phosphorylation","volume":"45","author":"Perea","year":"2018","journal-title":"Semin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1186\/s13046-019-1292-y","article-title":"Role of Protein Kinase CK2 in Antitumor Drug Resistance","volume":"38","author":"Borgo","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Firnau, M.-B., and Brieger, A. (2022). CK2 and the Hallmarks of Cancer. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081987"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bruserud, \u00d8., and Reikvam, H. (2023). Casein Kinase 2 (CK2): A Possible Therapeutic Target in Acute Myeloid Leukemia. Cancers, 15.","DOI":"10.3390\/cancers15143711"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s11010-022-04558-2","article-title":"Protein Kinase CK2\u2013Diverse Roles in Cancer Cell Biology and Therapeutic Promise","volume":"478","author":"Trembley","year":"2023","journal-title":"Mol. Cell. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"135814","DOI":"10.1016\/j.ijbiomac.2024.135814","article-title":"A Comprehensive Review on the Dynamics of Protein Kinase CK2 in Cancer Development and Optimizing Therapeutic Strategies","volume":"280","author":"Ghani","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1158\/1535-7163.MCT-08-1056","article-title":"Anticancer Peptide CIGB-300 Binds to Nucleophosmin\/B23, Impairs Its CK2-Mediated Phosphorylation, and Leads to Apoptosis through Its Nucleolar Disassembly Activity","volume":"8","author":"Perera","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/psc.1432","article-title":"Sensitivity of Tumor Cells towards CIGB-300 Anticancer Peptide Relies on Its Nucleolar Localization","volume":"18","author":"Perera","year":"2012","journal-title":"J. Pept. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.lungcan.2016.05.026","article-title":"CIGB-300, an Anti-CK2 Peptide, Inhibits Angiogenesis, Tumor Cell Invasion and Metastasis in Lung Cancer Models","volume":"107","author":"Capobianco","year":"2017","journal-title":"Lung Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26038","DOI":"10.1038\/s41598-024-75990-1","article-title":"CIGB-300 Internalizes and Impairs Viability of NSCLC Cells Lacking Actionable Targets by Inhibiting Casein Kinase-2 Signaling","volume":"14","author":"Yi","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1016\/j.yexcr.2011.04.011","article-title":"CIGB-300, a Proapoptotic Peptide, Inhibits Angiogenesis In Vitro and In Vivo","volume":"317","author":"Farina","year":"2011","journal-title":"Exp. Cell Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s11010-011-0950-y","article-title":"CIGB-300, a Synthetic Peptide-Based Drug That Targets the CK2 Phosphoaceptor Domain. Translational and Clinical Research","volume":"356","author":"Perea","year":"2011","journal-title":"Mol. Cell. Biochem."},{"key":"ref_28","unstructured":"(2025, December 05). Open Clinical Trial, Uncontrolled in Patients Bearing Squamous Cell Carcinoma or Adenocarcinoma of the Cervix Stage IIA and IIB FIGO Classification Treated with Radiotherapy External Endocavitary Brachytherapy + Concurrent Hemotherapy Weekly Systemic and Local Application of CIGB-300 Dose Escalation. Available online: https:\/\/go.drugbank.com\/drugs\/DB16464\/clinical_trials?conditions=DBCOND0029359%2CDBCOND0029361&phase=2&status=completed."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"14689","DOI":"10.1038\/s41598-020-71854-6","article-title":"Preclinical Efficacy of CIGB-300, an Anti-CK2 Peptide, on Breast Cancer Metastasic Colonization","volume":"10","author":"Gottardo","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3754","DOI":"10.4161\/cc.9.18.12933","article-title":"Recognition of P63 by the E3 Ligase ITCH: Effect of an Ectodermal Dysplasia Mutant","volume":"9","author":"Bellomaria","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.4161\/cc.21918","article-title":"Recognition Mechanism of P63 by the E3 Ligase Itch: Novel Strategy in the Study and Inhibition of This Interaction","volume":"11","author":"Bellomaria","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e3356","DOI":"10.1002\/psc.3356","article-title":"Formulation Matters! A Spectroscopic and Molecular Dynamics Investigation on the Peptide CIGB552 as Itself and in Its Therapeutical Formulation","volume":"28","author":"Savioli","year":"2022","journal-title":"J. Pept. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"W315","DOI":"10.1093\/nar\/gky497","article-title":"BeStSel: A Web Server for Accurate Protein Secondary Structure Prediction and Fold Recognition from the Circular Dichroism Spectra","volume":"46","author":"Micsonai","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Arciero, I., Buonvino, S., Palumbo, V., Scimeca, M., and Melino, S. (2024). A 3D-Printable Cell Array for In Vitro Breast Cancer Modeling. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252313068"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/jbm.a.35899","article-title":"PEG-Fibrinogen Hydrogels for Three-Dimensional Breast Cancer Cell Culture","volume":"105","author":"Pradhan","year":"2017","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s11658-021-00305-5","article-title":"The Interaction of Canonical Wnt\/\u03b2-Catenin Signaling with Protein Lysine Acetylation","volume":"27","author":"You","year":"2022","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lavrentev, F.V., Shilovskikh, V.V., Alabusheva, V.S., Yurova, V.Y., Nikitina, A.A., Ulasevich, S.A., and Skorb, E.V. (2023). Diffusion-Limited Processes in Hydrogels with Chosen Applications from Drug Delivery to Electronic Components. Molecules, 28.","DOI":"10.3390\/molecules28155931"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sheth, S., Barnard, E., Hyatt, B., Rathinam, M., and Zustiak, S.P. (2019). Predicting Drug Release from Degradable Hydrogels Using Fluorescence Correlation Spectroscopy and Mathematical Modeling. Front. Bioeng. Biotechnol., 7.","DOI":"10.3389\/fbioe.2019.00410"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1039\/C8SM02153H","article-title":"Monolithic Intercalated PNIPAm\/Starch Hydrogels with Very Fast and Extensive One-Way Volume and Swelling Responses to Temperature and pH: Prospective Actuators and Drug Release Systems","volume":"15","author":"Strachota","year":"2019","journal-title":"Soft Matter"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mser.2015.04.001","article-title":"Stimulus-Responsive Hydrogels: Theory, Modern Advances, and Applications","volume":"93","author":"Koetting","year":"2015","journal-title":"Mater. Sci. Eng. R Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1039\/C7CS00638A","article-title":"Hydrogels: Experimental Characterization and Mathematical Modelling of Their Mechanical and Diffusive Behaviour","volume":"47","author":"Caccavo","year":"2018","journal-title":"Chem. Soc. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e202200081","DOI":"10.1002\/asia.202200081","article-title":"Supramolecular Hydrogels: Design Strategies and Contemporary Biomedical Applications","volume":"17","author":"Omar","year":"2022","journal-title":"Chem. Asian J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"918","DOI":"10.4161\/cbt.4.9.2072","article-title":"Nucleophosmin\/B23, a Multifunctional Protein That Can Regulate Apoptosis","volume":"4","author":"Ye","year":"2005","journal-title":"Cancer Biol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21009","DOI":"10.1074\/jbc.270.36.21009","article-title":"Role of Protein Phosphorylation in Post-Translational Regulation of Protein B23 during Programmed Cell Death in the Prostate Gland","volume":"270","author":"Tawfic","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5473","DOI":"10.1021\/pr100728v","article-title":"Proteomic Profile Regulated by the Anticancer Peptide CIGB-300 in Non-Small Cell Lung Cancer (NSCLC) Cells","volume":"9","author":"Ramos","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"44821","DOI":"10.18632\/oncotarget.8599","article-title":"Molecules That Target Nucleophosmin for Cancer Treatment: An Update","volume":"7","author":"Franceschini","year":"2016","journal-title":"Oncotarget"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Cela, I., Di Matteo, A., and Federici, L. (2020). Nucleophosmin in Its Interaction with Ligands. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21144885"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"21443","DOI":"10.18632\/oncotarget.4167","article-title":"NPM1 Activates Metabolic Changes by Inhibiting FBP1 While Promoting the Tumorigenicity of Pancreatic Cancer Cells","volume":"6","author":"Zhu","year":"2015","journal-title":"Oncotarget"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.1038\/sj.onc.1210942","article-title":"Influence of Nucleophosmin\/B23 on DNA Binding and Transcriptional Activity of the Androgen Receptor in Prostate Cancer Cell","volume":"27","author":"Meunier","year":"2008","journal-title":"Oncogene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/sj.bjc.6603574","article-title":"Increased Expression of Nucleophosmin\/B23 in Hepatocellular Carcinoma and Correlation with Clinicopathological Parameters","volume":"96","author":"Yun","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.bbrc.2015.08.118","article-title":"Upregulation of B23 Promotes Tumor Cell Proliferation and Predicts Poor Prognosis in Glioma","volume":"466","author":"Chen","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"16495","DOI":"10.1038\/srep16495","article-title":"NPM1 Histone Chaperone Is Upregulated in Glioblastoma to Promote Cell Survival and Maintain Nucleolar Shape","volume":"5","author":"Elsir","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/apm.12381","article-title":"Nucleophosmin Overexpression Is Associated with Poor Survival in Astrocytoma","volume":"123","author":"Kuo","year":"2015","journal-title":"APMIS"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.bbrc.2010.05.142","article-title":"Nucleophosmin Is Overexpressed in Thyroid Tumors","volume":"397","author":"Pianta","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","first-page":"3372","article-title":"Genes Preferentially Expressed in Embryo Stomach Are Predominantly Expressed in Gastric Cancer","volume":"52","author":"Tanaka","year":"1992","journal-title":"Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/(SICI)1096-9896(199601)178:1<48::AID-PATH432>3.0.CO;2-Y","article-title":"Expression of Nucleophosmin\/B23 in Normal and Neoplastic Colorectal Mucosa","volume":"178","author":"Nozawa","year":"1996","journal-title":"J. Pathol."},{"key":"ref_57","first-page":"285","article-title":"Oncogenic Role of Nucleophosmin\/B23","volume":"30","author":"Yung","year":"2007","journal-title":"Chang Gung Med. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1038\/onc.2010.646","article-title":"Nucleophosmin and Its Complex Network: A Possible Therapeutic Target in Hematological Diseases","volume":"30","author":"Colombo","year":"2011","journal-title":"Oncogene"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1475-2867-5-30","article-title":"ABC Transporters as Multidrug Resistance Mechanisms and the Development of Chemosensitizers for Their Reversal","volume":"5","author":"Choi","year":"2005","journal-title":"Cancer Cell Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/ijc.21297","article-title":"Involvement of P-glycoprotein and MRP1 in Resistance to Cyclic Tetrapeptide Subfamily of Histone Deacetylase Inhibitors in the Drug-resistant Osteosarcoma and Ewing\u2019s Sarcoma Cells","volume":"118","author":"Okada","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.imbio.2014.10.015","article-title":"Decreased Expression of Nucleophosmin\/B23 Increases Drug Sensitivity of Adriamycin-Resistant Molt-4 Leukemia Cells through Mdr-1 Regulation and Akt\/mTOR Signaling","volume":"220","author":"Wang","year":"2015","journal-title":"Immunobiology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.ijbiomac.2017.11.013","article-title":"Injectable Silk Fibroin Hydrogels Functionalized with Microspheres as Adult Stem Cells-Carrier Systems","volume":"108","author":"Ciocci","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_63","unstructured":"Garibbo, A., Boragno, C., and Gagliardi, F. (2015). Process for the Preparation of Superhydrophobic Film. (20120181717A1), U.S. Patent, Available online: https:\/\/patents.google.com\/patent\/US20120181717A1\/en?oq=US20120181717A1."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1007\/s10616-015-9909-2","article-title":"A Comparative Study of Colorimetric Cell Proliferation Assays in Immune Cells","volume":"68","author":"Koyanagi","year":"2016","journal-title":"Cytotechnology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1973\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T05:13:36Z","timestamp":1771650816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":64,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27041973"],"URL":"https:\/\/doi.org\/10.3390\/ijms27041973","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]}}}