title: Knockdown of osteopontin chemosensitizes MDA-MB-231 cells to cyclophosphamide by enhancing apoptosis through activating p38 MAPK pathway.
abstract: Cyclophosphamide (CTX) is a commonly used chemotherapeutic agent for breast cancer. However, chemoresistance remains a common clinical problem. Osteopontin (OPN) has been shown to induce chemoresistance by inhibiting apoptosis; p38 MAPK pathway has been reported to be involved in chemotherapy-induced apoptosis. Thus, this study investigated whether OPN knockdown would chemosensitize MDA-MB-231 cells to CTX by enhancing apoptosis through activating p38 MAPK pathway. MDA-MB-231 cells were transfected with OPN stable siRNA plasmid, and it was found that OPN knockdown chemosensitized MDA-MB-231 cells to CTX, which is dependent on p38 MAPK pathway activation. Moreover, results showed that each of OPN knockdown and CTX could induce apoptosis through activating p38 MAPK pathway and that OPN knockdown and CTX could induce enhanced apoptosis through activating p38 MAPK pathway synergistically. Therefore, this study concludes that OPN knockdown chemosensitizes MDA-MB-231 cells to CTX by enhancing apoptosis through activating p38 MAPK pathway.
authors.affiliation: Department of Oncology Medicine, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China. phgr2010@163.com
authors.forename: Hui
authors.initials: H
authors.lastname: Pang
authors.forename: Li
authors.initials: L
authors.lastname: Cai
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Yang
authors.forename: Xuesong
authors.initials: X
authors.lastname: Chen
authors.forename: Guangjie
authors.initials: G
authors.lastname: Sui
authors.forename: Changhong
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D053495:Osteopontin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D053495:Osteopontin; D003520:Cyclophosphamide; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human