{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T12:11:54Z","timestamp":1780920714285,"version":"3.54.1"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":67,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Treatment and Research Communications"],"published-print":{"date-parts":[[2026]]},"DOI":"10.1016\/j.ctarc.2026.101172","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T08:17:05Z","timestamp":1773130625000},"page":"101172","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Apoptosis induction and migration suppression through regulation of IGF-1R\/FoxO signaling pathways in Panc1 pancreatic cancer cells by hAMSCs secretome: An in vitro cell-based therapy"],"prefix":"10.1016","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0300-7665","authenticated-orcid":false,"given":"Fatemeh","family":"Safari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Rasouli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mana","family":"Alavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ctarc.2026.101172_bib0001","article-title":"Palmitoyl carnitine-anchored nanoliposomes for neovasculature-specific delivery of gemcitabine elaidate to treat pancreatic cancer","volume":"15","author":"Patel","year":"2023","journal-title":"Cancers. (Basel)"},{"key":"10.1016\/j.ctarc.2026.101172_bib0002","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3390\/cancers10020048","article-title":"Early diagnosis to improve the poor prognosis of pancreatic cancer","volume":"10","author":"Kikuyama","year":"2018","journal-title":"Cancers. (Basel)"},{"key":"10.1016\/j.ctarc.2026.101172_bib0003","doi-asserted-by":"crossref","first-page":"615","DOI":"10.3109\/14653241003631815","article-title":"Mesenchymal stromal cells alone or expressing interferon-\u03b2 suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment","volume":"12","author":"Kidd","year":"2010","journal-title":"Cytotherapy."},{"key":"10.1016\/j.ctarc.2026.101172_bib0004","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0006278","article-title":"Adult stromal cells derived from Human adipose tissue provoke pancreatic cancer cell death both In vitro and In vivo","volume":"4","author":"Cousin","year":"2009","journal-title":"PLoS. One"},{"key":"10.1016\/j.ctarc.2026.101172_bib0005","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/s13287-022-02910-3","article-title":"Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model","volume":"13","author":"Chen","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"10.1016\/j.ctarc.2026.101172_bib0006","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s13770-018-0128-8","article-title":"The use of normal stem cells and cancer stem cells for potential anti-cancer therapeutic strategy","volume":"15","author":"Han","year":"2018","journal-title":"Tissue Eng. Regen. Med."},{"key":"10.1016\/j.ctarc.2026.101172_bib0007","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2024.113265","article-title":"Exploring the dichotomy of the mesenchymal stem cell secretome: implications for tumor modulation via cell-signaling pathways","volume":"143","author":"Rasouli","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ctarc.2026.101172_bib0008","doi-asserted-by":"crossref","DOI":"10.1016\/j.tice.2020.101479","article-title":"Evaluating the in vitro therapeutic effects of human amniotic mesenchymal stromal cells on MiaPaca2 pancreatic cancer cells using 2D and 3D cell culture model","volume":"68","author":"Rahmani","year":"2021","journal-title":"Tissue Cell"},{"key":"10.1016\/j.ctarc.2026.101172_bib0009","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.1038\/sj.onc.1203854","article-title":"The contradictions of the insulin-like growth factor 1 receptor","volume":"19","author":"Baserga","year":"2000","journal-title":"Oncogene"},{"key":"10.1016\/j.ctarc.2026.101172_bib0010","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.tcb.2008.07.004","article-title":"Unravelling the tumor suppressive functions of FOXO proteins","volume":"18","author":"Dansen","year":"2008","journal-title":"Trends. Cell Biol."},{"key":"10.1016\/j.ctarc.2026.101172_bib0011","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/bs.ctdb.2017.10.006","article-title":"Regulation of FOXO factors in mammalian cells","volume":"127","author":"Brown","year":"2018","journal-title":"Curr. Top. Dev. Biol."},{"key":"10.1016\/j.ctarc.2026.101172_bib0012","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/sj.bjp.0707161","article-title":"Erythropoietin involves the phosphatidylinositol 3-kinase pathway, 14-3-3 protein and FOXO3a nuclear trafficking to preserve endothelial cell integrity","volume":"150","author":"Chong","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ctarc.2026.101172_bib0013","doi-asserted-by":"crossref","first-page":"39152","DOI":"10.1074\/jbc.M002417200","article-title":"Insulin-like growth factor-1-induced phosphorylation of the forkhead Family transcription factor FKHRL1 is mediated by Akt Kinase in PC12 cells","volume":"275","author":"Zheng","year":"2000","journal-title":"J. Biological Chem."},{"key":"10.1016\/j.ctarc.2026.101172_bib0014","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1016\/j.biopha.2016.11.027","article-title":"Elucidating the role of the FoxO3a transcription factor in the IGF-1-induced migration and invasion of uveal melanoma cancer cells","volume":"84","author":"Yan","year":"2016","journal-title":"Biomed. PharmacOther"},{"issue":"2007","key":"10.1016\/j.ctarc.2026.101172_bib0015","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.cell.2006.12.029","article-title":"FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis","volume":"128","author":"Paik","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.ctarc.2026.101172_bib0016","doi-asserted-by":"crossref","first-page":"9018","DOI":"10.1158\/0008-5472.CAN-07-1691","article-title":"Trastuzumab-resistant HER2-driven breast cancer cells are sensitive to epigallocatechin-3 gallate","volume":"67","author":"Eddy","year":"2007","journal-title":"Cancer Res."},{"key":"10.1016\/j.ctarc.2026.101172_bib0017","doi-asserted-by":"crossref","first-page":"47928","DOI":"10.1074\/jbc.M207509200","article-title":"FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer","volume":"277","author":"Modur","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ctarc.2026.101172_bib0018","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1158\/1541-7786.MCR-04-0163","article-title":"The progression of LNCaP human prostate cancer cells to androgen independence involves decreased FOXO3a expression and reduced p27KIP1 promoter transactivation","volume":"3","author":"Lynch","year":"2005","journal-title":"Mol. Cancer Res."},{"key":"10.1016\/j.ctarc.2026.101172_bib0019","doi-asserted-by":"crossref","first-page":"4917","DOI":"10.1128\/MCB.01789-06","article-title":"Induction of Mxi1-SR alpha by FOXO3a contributes to repression of myc-dependent gene expression","volume":"27","author":"Delpuech","year":"2007","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.ctarc.2026.101172_bib0020","doi-asserted-by":"crossref","first-page":"7081","DOI":"10.1038\/sj.onc.1210519","article-title":"Homeostatic chemokines increase survival of B-chronic lymphocytic leukemia cells through inactivation of transcription factor FOXO3a","volume":"26","author":"Ticchioni","year":"2007","journal-title":"Oncogene"},{"key":"10.1016\/j.ctarc.2026.101172_bib0021","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1210\/en.2003-1199","article-title":"Inhibition of phosphorylation of a forkhead transcription factor sensitizes human ovarian cancer cells to cisplatin","volume":"145","author":"Arimoto-Ishida","year":"2004","journal-title":"Endocrinology"},{"key":"10.1016\/j.ctarc.2026.101172_bib0022","doi-asserted-by":"crossref","first-page":"3457","DOI":"10.1128\/MCB.05523-11","article-title":"Cdc25A regulates matrix metalloprotease 1 through Foxo1 and mediates metastasis of breast cancer cells","volume":"31","author":"Feng","year":"2011","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.ctarc.2026.101172_bib0023","doi-asserted-by":"crossref","first-page":"4906","DOI":"10.1128\/MCB.00077-09","article-title":"FOXO3a promotes tumor cell invasion through the induction of matrix metalloproteinases","volume":"29","author":"Storz","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.ctarc.2026.101172_bib0024","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.semcancer.2017.11.017","article-title":"Re-evaluating the role of FOXOs in cancer","volume":"50","author":"Hornsveld","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"10.1016\/j.ctarc.2026.101172_bib0025","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1038\/s41467-021-23052-9","article-title":"Disruption of FOXO3a-miRNA feedback inhibition of IGF2\/IGF-1R\/IRS1 signaling confers herceptin resistance in HER2-positive breast cancer","volume":"12","author":"Luo","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ctarc.2026.101172_bib0026","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/1471-2202-5-48","article-title":"Foxo3a induces motoneuron death through the Fas pathway in cooperation with JNK","volume":"5","author":"Barth\u00e9l\u00e9my","year":"2004","journal-title":"BMC. Neurosci."},{"key":"10.1016\/j.ctarc.2026.101172_bib0027","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1038\/sj.onc.1207456","article-title":"FLT3 receptors with internal tandem duplications promote cell viability and proliferation by signaling through Foxo proteins","volume":"23","author":"Scheijen","year":"2004","journal-title":"Oncogene"},{"key":"10.1016\/j.ctarc.2026.101172_bib0028","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1158\/0008-5472.CAN-05-1018","article-title":"RNA interference-mediated depletion of phosphoinositide 3-kinase activates forkhead box class O transcription factors and induces cell cycle arrest and apoptosis in breast carcinoma cells","volume":"66","author":"Reagan-Shaw","year":"2006","journal-title":"Cancer Res."},{"key":"10.1016\/j.ctarc.2026.101172_bib0029","article-title":"FOXO transcription factors: their clinical significance and regulation","author":"Wang","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"10.1016\/j.ctarc.2026.101172_bib0030","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.4081\/oncol.2013.e3","article-title":"Modulation of insulin-like growth factor-1 receptor and its signaling network for the treatment of cancer: current status and future perspectives","volume":"7","author":"Jin","year":"2013","journal-title":"Oncol. Rev."},{"key":"10.1016\/j.ctarc.2026.101172_bib0031","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1158\/1535-7163.MCT-06-0080","article-title":"Disrupting insulin-like growth factor signaling as a potential cancer therapy","volume":"6","author":"Sachdev","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.ctarc.2026.101172_bib0032","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s11523-012-0248-3","article-title":"Prognostic and therapeutic relevance of the IGF pathway in Ewing\u2019s sarcoma patients","volume":"8","author":"van de Luijtgaarden","year":"2013","journal-title":"Target. Oncol."},{"key":"10.1016\/j.ctarc.2026.101172_bib0033","doi-asserted-by":"crossref","first-page":"6541","DOI":"10.1002\/j.1460-2075.1996.tb01045.x","article-title":"Mechanism of activation of protein kinase B by insulin and IGF-1","volume":"15","author":"Alessi","year":"1996","journal-title":"EMBOJ"},{"key":"10.1016\/j.ctarc.2026.101172_bib0034","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s12032-022-01649-4","article-title":"The inhibition of Panc1 cancer cells invasion by hAMSCs secretome through suppression of tyrosine phosphorylation of SGK223 (at Y411 site), c-src (at Y416, Y530 sites), AKT activity, and JAK1\/Stat3 signaling","volume":"39","author":"Safari","year":"2022","journal-title":"Med. Oncol."},{"key":"10.1016\/j.ctarc.2026.101172_bib0035","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3389\/fendo.2015.00092","article-title":"Crosstalk of the insulin-like growth factor receptor with the Wnt signaling pathway in breast cancer","volume":"6","author":"Rota","year":"2015","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"10.1016\/j.ctarc.2026.101172_bib0036","doi-asserted-by":"crossref","first-page":"815","DOI":"10.7150\/ijbs.20052","article-title":"FOXO signaling pathways as therapeutic targets in cancer","volume":"13","author":"Farhan","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.ctarc.2026.101172_bib0037","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1128\/MCB.22.7.2025-2036.2002","article-title":"Control of cell cycle exit and entry by protein kinase B-regulated forkhead transcription factors","volume":"22","author":"Kops","year":"2002","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.ctarc.2026.101172_bib0038","doi-asserted-by":"crossref","first-page":"21960","DOI":"10.1074\/jbc.M000759200","article-title":"Inhibition of the phosphoinositide 3-kinase pathway induces a senescence-like arrest mediated by p27Kip1","volume":"275","author":"Collado","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ctarc.2026.101172_bib0039","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1007\/s12094-022-03067-4","article-title":"Theraputic effects of hAMSCs secretome on proliferation of MDA-MB-231breast cancer cells by the cell cycle arrest in G\/S phase","volume":"25","author":"Rahimi Lifshagerd","year":"2023","journal-title":"Clin. Trans. Oncol"},{"key":"10.1016\/j.ctarc.2026.101172_bib0040","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1158\/1078-0432.CCR-02-1441","article-title":"Prognostic significance of activated akt expression in pancreatic ductal adenocarcinoma","volume":"10","author":"Yamamoto","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ctarc.2026.101172_bib0041","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.7150\/jca.28299","article-title":"AMPK inhibition suppresses the malignant phenotype of pancreatic cancer cells in part by attenuating aerobic glycolysis","volume":"10","author":"Hu","year":"2019","journal-title":"J. Cancer"},{"key":"10.1016\/j.ctarc.2026.101172_bib0042","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.18632\/oncotarget.13786","article-title":"FOXO1 inhibits the invasion and metastasis ofhepatocellular carcinoma by reversing ZEB2-induced epithelial-mesenchymal transition","volume":"8","author":"Dong","year":"2017","journal-title":"Oncotarget."},{"key":"10.1016\/j.ctarc.2026.101172_bib0043","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1172\/JCI90077","article-title":"Geminin facilitates FoxO3 deacetylation to promote breast cancer cell metastasis","volume":"127","author":"Zhang","year":"2017","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ctarc.2026.101172_bib0044","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13046-019-1046-x","article-title":"Knockdown of FOXO3a induces epithelial mesenchymal transition and promotes metastasis of pancreatic ductal adenocarcinoma by activation of the beta-catenin\/TCF4 pathway through SPRY2","volume":"38","author":"Li","year":"2019","journal-title":"J. Experim. Clin. Cancer Res."},{"key":"10.1016\/j.ctarc.2026.101172_bib0045","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1158\/1078-0432.CCR-13-1687","article-title":"Down regulation of FOXO3a promotes tumor metastasis and is associated with metastasis-free survival of patients with clear cell renal cell carcinoma","volume":"20","author":"Ni","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ctarc.2026.101172_bib0046","doi-asserted-by":"crossref","first-page":"4424","DOI":"10.1091\/mbc.e10-12-0971","article-title":"NOX4 mediates activation of FoxO3a and matrix metalloproteinase-2 expression by urotensin-II","volume":"22","author":"Diebold","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.ctarc.2026.101172_bib0047","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1161\/ATVBAHA.117.310502","article-title":"FOXO3a (forkhead transcription factor O subfamily member 3a) links vascular smooth muscle cell apoptosis, matrix breakdown, atherosclerosis, and vascular remodeling through a novel pathway involving MMP13 (matrix metalloproteinase 13)","volume":"38","author":"Yu","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.ctarc.2026.101172_bib0048","doi-asserted-by":"crossref","first-page":"5145","DOI":"10.2147\/CMAR.S157661","article-title":"Downregulation of FOXO6 in breast cancer promotes epithelial-mesenchymal transition and facilitates migration and proliferation of cancer cells","volume":"10","author":"Ye","year":"2018","journal-title":"Cancer Manage Res."}],"container-title":["Cancer Treatment and Research Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2468294226000833?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2468294226000833?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:49:36Z","timestamp":1780919376000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2468294226000833"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":48,"alternative-id":["S2468294226000833"],"URL":"https:\/\/doi.org\/10.1016\/j.ctarc.2026.101172","relation":{},"ISSN":["2468-2942"],"issn-type":[{"value":"2468-2942","type":"print"}],"subject":[],"published":{"date-parts":[[2026]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Apoptosis induction and migration suppression through regulation of IGF-1R\/FoxO signaling pathways in Panc1 pancreatic cancer cells by hAMSCs secretome: An in vitro cell-based therapy","name":"articletitle","label":"Article Title"},{"value":"Cancer Treatment and Research Communications","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ctarc.2026.101172","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"101172"}}