{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T22:17:41Z","timestamp":1784326661082,"version":"3.55.0"},"reference-count":61,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T00:00:00Z","timestamp":1625270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006772","name":"Max and Minnie Tomerlin Voelcker Fund","doi-asserted-by":"publisher","award":["163849"],"award-info":[{"award-number":["163849"]}],"id":[{"id":"10.13039\/100006772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP 170345"],"award-info":[{"award-number":["RP 170345"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Ovarian cancer often has a poor clinical prognosis because of late detection, frequently after metastatic progression, as well as acquired resistance to taxane-based therapy. Herein, we evaluate a novel class of covalent microtubule stabilizers, the C-22,23-epoxytaccalonolides, for their efficacy against taxane-resistant ovarian cancer models in vitro and in vivo. Taccalonolide AF, which covalently binds \u03b2-tubulin through its C-22,23-epoxide moiety, demonstrates efficacy against taxane-resistant models and shows superior persistence in clonogenic assays after drug washout due to irreversible target engagement. In vivo, intraperitoneal administration of taccalonolide AF demonstrated efficacy against the taxane-resistant NCI\/ADR-RES ovarian cancer model both as a flank xenograft, as well as in a disseminated orthotopic disease model representing localized metastasis. Taccalonolide-treated animals had a significant decrease in micrometastasis of NCI\/ADR-RES cells to the spleen, as detected by quantitative RT-PCR, without any evidence of systemic toxicity. Together, these findings demonstrate that taccalonolide AF retains efficacy in taxane-resistant ovarian cancer models in vitro and in vivo and that its irreversible mechanism of microtubule stabilization has the unique potential for intraperitoneal treatment of locally disseminated taxane-resistant disease, which represents a significant unmet clinical need in the treatment of ovarian cancer patients.<\/jats:p>","DOI":"10.3390\/molecules26134077","type":"journal-article","created":{"date-parts":[[2021,7,4]],"date-time":"2021-07-04T22:34:36Z","timestamp":1625438076000},"page":"4077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy of a Covalent Microtubule Stabilizer in Taxane-Resistant Ovarian Cancer Models"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7953-0183","authenticated-orcid":false,"given":"Samantha S.","family":"Yee","sequence":"first","affiliation":[{"name":"Department of Pharmacology, The University of Texas Health Science Center at San Antonio, Floyd Curl Drive, San Antonio, TX 78229, USA"},{"name":"Mays Cancer Center, 7979 Wurzbach Road, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4363-3268","authenticated-orcid":false,"given":"April L.","family":"Risinger","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, The University of Texas Health Science Center at San Antonio, Floyd Curl Drive, San Antonio, TX 78229, USA"},{"name":"Mays Cancer Center, 7979 Wurzbach Road, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41586-019-1456-0","article-title":"CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy","volume":"572","author":"Barkal","year":"2019","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s42003-020-01246-z","article-title":"Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1","volume":"3","author":"Krishnan","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_4","first-page":"142","article-title":"Greater Omental Pancake Tumour due to Metastasis of Ovarian Cancer\u2014A Cadaveric Study","volume":"8","author":"Bhusari","year":"2014","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/s41416-020-0763-4","article-title":"Genetic heterogeneity and evolutionary history of high-grade ovarian carcinoma and matched distant metastases","volume":"122","author":"Masoodi","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1188\/16.CJON.169-173","article-title":"Caregiver Burden in End-Stage Ovarian Cancer","volume":"20","author":"Hartnett","year":"2016","journal-title":"Clin. J. Oncol. Nurs."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"van Stein, R.M., Aalbers, A.G.J., Sonke, G.S., and van Driel, W.J. (2021). Hyperthermic Intraperitoneal Chemotherapy for Ovarian and Colorectal Cancer: A Review. JAMA Oncol.","DOI":"10.1001\/jamaoncol.2021.0580"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.21037\/gs-2019-ursoc-11","article-title":"Rotational intraperitoneal pressurized aerosol chemotherapy in a porcine model","volume":"10","author":"Mun","year":"2021","journal-title":"Gland Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1158\/1535-7163.MCT-13-0791","article-title":"Targeting microtubules by natural agents for cancer therapy","volume":"13","author":"Mukhtar","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4546","DOI":"10.1002\/jcp.26289","article-title":"Molecular mechanisms of drug resistance in ovarian cancer","volume":"233","author":"Sarookhani","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41698-018-0063-0","article-title":"Tumor evolution and chemoresistance in ovarian cancer","volume":"2","author":"Kim","year":"2018","journal-title":"NPJ Precis. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Xiao, X., Zou, J., Fang, Y., Meng, Y., Xiao, C., Fu, J., Liu, S., Bai, P., and Yao, Y. (2018). Fisetin and polymeric micelles encapsulating fisetin exhibit potent cytotoxic effects towards ovarian cancer cells. BMC Complement. Altern. Med., 18.","DOI":"10.1186\/s12906-018-2127-7"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1093\/jnci\/92.3.182","article-title":"Tubulin\/microtubules: Still a promising target for new chemotherapeutic agents","volume":"92","author":"Giannakakou","year":"2000","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3892\/ol.2020.12001","article-title":"Antitumor effects and molecular mechanisms of action of natural products in ovarian cancer","volume":"20","author":"Yan","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.canlet.2017.09.050","article-title":"The use of natural compounds for the targeting and chemoprevention of ovarian cancer","volume":"411","author":"Pistollato","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/s41467-019-14277-w","article-title":"Elucidating target specificity of the taccalonolide covalent microtubule stabilizers employing a combinatorial chemical approach","volume":"11","author":"Du","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15787","DOI":"10.1038\/ncomms15787","article-title":"Mechanism of microtubule stabilization by taccalonolide AJ","volume":"8","author":"Wang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6780","DOI":"10.1158\/0008-5472.CAN-13-1346","article-title":"Taccalonolide binding to tubulin imparts microtubule stability and potent in vivo activity","volume":"73","author":"Risinger","year":"2013","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1021\/acs.jnatprod.6b00944","article-title":"Pharmacokinetic Analysis and in Vivo Antitumor Efficacy of Taccalonolides AF and AJ","volume":"80","author":"Risinger","year":"2017","journal-title":"J. Nat. Prod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1021\/acs.jnatprod.7b00967","article-title":"Taccalonolide Microtubule Stabilizers Generated Using Semisynthesis Define the Effects of Mono Acyloxy Moieties at C-7 or C-15 and Disubstitutions at C-7 and C-25","volume":"81","author":"Ola","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_21","first-page":"103209","article-title":"Systemic treatment of newly diagnosed advanced epithelial ovarian cancer: From chemotherapy to precision medicine","volume":"158","author":"Grau","year":"2020","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1586\/14737140.1.1.142","article-title":"Intraperitoneal chemotherapy in the management of malignant disease","volume":"1","author":"Markman","year":"2001","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_23","first-page":"1","article-title":"Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer","volume":"62","author":"Dedrick","year":"1978","journal-title":"Cancer Treat. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/0024-3205(95)02200-7","article-title":"Pharmacokinetic and pharmacodynamic optimization of intraperitoneal chemotherapy","volume":"58","author":"Balthasar","year":"1996","journal-title":"Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Jaaback, K., and Johnson, N. (2006). Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD005340.pub2"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/j.1525-1438.2006.00846.x","article-title":"A meta-analysis of the efficacy of intraperitoneal cisplatin for the front-line treatment of ovarian cancer","volume":"17","author":"Hess","year":"2007","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/BF00686048","article-title":"Platinum distribution in intraperitoneal tumors after intraperitoneal cisplatin treatment","volume":"25","author":"Los","year":"1990","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.critrevonc.2019.01.002","article-title":"Role of intraperitoneal chemotherapy in ovarian cancer in the platinum-taxane-based era: A meta-analysis","volume":"136","author":"Marchetti","year":"2019","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6141","DOI":"10.1021\/jm500619j","article-title":"Synthetic reactions with rare taccalonolides reveal the value of C-22,23 epoxidation for microtubule stabilizing potency","volume":"57","author":"Peng","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ygyno.2013.07.107","article-title":"ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas","volume":"131","author":"Johnatty","year":"2013","journal-title":"Gynecol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.biopha.2018.02.038","article-title":"Understanding of human ATP binding cassette superfamily and novel multidrug resistance modulators to overcome MDR","volume":"100","author":"Mohammad","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bender, J., Fang, J., and Simon, R. (2017). A computational study of the inhibition mechanisms of P-glycoprotein mediated paclitaxel efflux by kinase inhibitors. BMC Syst. Biol., 11.","DOI":"10.1186\/s12918-017-0498-x"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8881","DOI":"10.1158\/0008-5472.CAN-08-2037","article-title":"The taccalonolides: Microtubule stabilizers that circumvent clinically relevant taxane resistance mechanisms","volume":"68","author":"Risinger","year":"2008","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.canlet.2006.01.013","article-title":"A case study in misidentification of cancer cell lines: MCF-7\/AdrR cells (re-designated NCI\/ADR-RES) are derived from OVCAR-8 human ovarian carcinoma cells","volume":"245","author":"Liscovitch","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3389\/fgene.2020.00516","article-title":"MDR1 Gene Polymorphisms and Its Association With Expression as a Clinical Relevance in Terms of Response to Chemotherapy and Prognosis in Ovarian Cancer","volume":"11","author":"Haque","year":"2020","journal-title":"Front. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100754","DOI":"10.1016\/j.drup.2021.100754","article-title":"Therapeutic strategies to overcome taxane resistance in cancer","volume":"55","author":"Das","year":"2021","journal-title":"Drug Resist. Updat."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lisio, M.A., Fu, L., Goyeneche, A., Gao, Z.H., and Telleria, C. (2019). High-Grade Serous Ovarian Cancer: Basic Sciences, Clinical and Therapeutic Standpoints. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040952"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Anglesio, M.S., Wiegand, K.C., Melnyk, N., Chow, C., Salamanca, C., Prentice, L.M., Senz, J., Yang, W., Spillman, M.A., and Cochrane, D.R. (2013). Type-specific cell line models for type-specific ovarian cancer research. PLoS ONE, 8.","DOI":"10.1371\/annotation\/ffcaf179-872f-470b-8bb6-f06d8ba6d03a"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"46120","DOI":"10.18632\/oncotarget.10028","article-title":"Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines","volume":"7","author":"Kloudova","year":"2016","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Beaufort, C.M., Helmijr, J.C., Piskorz, A.M., Hoogstraat, M., Ruigrok-Ritstier, K., Besselink, N., Murtaza, M., van, I.W.F., Heine, A.A., and Smid, M. (2014). Ovarian cancer cell line panel (OCCP): Clinical importance of in vitro morphological subtypes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103988"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1136\/jclinpath-2014-202430","article-title":"Caution over use of ES2 as a model of ovarian clear cell carcinoma","volume":"67","author":"Kwok","year":"2014","journal-title":"J. Clin. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tudrej, P., Olbryt, M., Zembala-Nozynska, E., Kujawa, K.A., Cortez, A.J., Fiszer-Kierzkowska, A., Piglowski, W., Nikiel, B., Glowala-Kosinska, M., and Bartkowska-Chrobok, A. (2018). Establishment and Characterization of the Novel High-Grade Serous Ovarian Cancer Cell Line OVPA8. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072080"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1038\/ncomms3126","article-title":"Evaluating cell lines as tumour models by comparison of genomic profiles","volume":"4","author":"Domcke","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12935-015-0263-4","article-title":"High-grade serous ovarian cancer cell lines exhibit heterogeneous responses to growth factor stimulation","volume":"15","author":"Bourgeois","year":"2015","journal-title":"Cancer Cell Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5515","DOI":"10.1038\/s41598-019-41941-4","article-title":"Ovarian cancer cell lines derived from non-serous carcinomas migrate and invade more aggressively than those derived from high-grade serous carcinomas","volume":"9","author":"Dawson","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10799","DOI":"10.1038\/s41598-020-67533-1","article-title":"Identification of ovarian high-grade serous carcinoma cell lines that show estrogen-sensitive growth as xenografts in immunocompromised mice","volume":"10","author":"Box","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"32810","DOI":"10.18632\/oncotarget.9053","article-title":"Functional characterization of a panel of high-grade serous ovarian cancer cell lines as representative experimental models of the disease","volume":"7","author":"Haley","year":"2016","journal-title":"Oncotarget"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.ygyno.2015.05.040","article-title":"In vivo tumor growth of high-grade serous ovarian cancer cell lines","volume":"138","author":"Mitra","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ebiom.2019.11.009","article-title":"Integrative proteogenomic analyses of human tumours identifies ADNP as a novel oncogenic mediator of cell cycle progression in high-grade serous ovarian cancer with poor prognosis","volume":"50","author":"Karagoz","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ygyno.2015.08.017","article-title":"Beyond genomics: Critical evaluation of cell line utility for ovarian cancer research","volume":"139","author":"Elias","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1158\/0008-5472.CAN-10-1874","article-title":"Eribulin induces irreversible mitotic blockade: Implications of cell-based pharmacodynamics for in vivo efficacy under intermittent dosing conditions","volume":"71","author":"Towle","year":"2011","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Sjoquist, K.M., Espinoza, D., Mileshkin, L., Ananda, S., Shannon, C., Yip, S., Goh, J., Bowtell, D., Harrison, M., and Friedlander, M.L. (2021). REZOLVE (ANZGOG-1101): A phase 2 trial of intraperitoneal bevacizumab to treat symptomatic ascites in patients with chemotherapy-resistant, epithelial ovarian cancer. Gynecol. Oncol.","DOI":"10.1016\/j.ygyno.2021.02.002"},{"key":"ref_53","unstructured":"Conway, G.D. (2019). The Role of Testisin and PAR-2 Signaling in Ovarian Cancer Metastasis. [Ph.D. Thesis, University of Maryland]."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Dahn, M.L., Dean, C.A., Jo, D.B., Coyle, K.M., and Marcato, P. (2020). Human-specific GAPDH RT-qPCR is an accurate and sensitive method of xenograft metastasis quantification. bioRxiv.","DOI":"10.1101\/2020.07.16.207175"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.21873\/invivo.11632","article-title":"Quality Indicators and Survival Outcome in Stage IIIB-IVB Epithelial Ovarian Cancer Treated at a Single Institution","volume":"33","author":"Steinberga","year":"2019","journal-title":"In Vivo"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1757-2215-4-21","article-title":"Gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin, paclitaxel, or doxorubicin","volume":"4","author":"Becker","year":"2011","journal-title":"J. Ovarian Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1056\/NEJM199601043340101","article-title":"Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer","volume":"334","author":"McGuire","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Balaguer, F.A., Muhlethaler, T., Estevez-Gallego, J., Calvo, E., Gimenez-Abian, J.F., Risinger, A.L., Sorensen, E.J., Vanderwal, C.D., Altmann, K.H., and Mooberry, S.L. (2019). Crystal Structure of the Cyclostreptin-Tubulin Adduct: Implications for Tubulin Activation by Taxane-Site Ligands. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061392"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/jcp.28967","article-title":"Potential drugs used in the antibody-drug conjugate (ADC) architecture for cancer therapy","volume":"235","author":"Yaghoubi","year":"2020","journal-title":"J. Cell Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/s41467-017-00962-1","article-title":"High grade serous ovarian carcinomas originate in the fallopian tube","volume":"8","author":"Papp","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.3390\/ijms11093039","article-title":"P-Glycoprotein\/MDR1 regulates pokemon gene transcription through p53 expression in human breast cancer cells","volume":"11","author":"He","year":"2010","journal-title":"Int. J. Mol. Sci."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/13\/4077\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:25:36Z","timestamp":1760163936000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/13\/4077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,3]]},"references-count":61,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["molecules26134077"],"URL":"https:\/\/doi.org\/10.3390\/molecules26134077","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,3]]}}}