title: Tubeimoside I sensitizes cisplatin in cisplatin-resistant human ovarian cancer cells (A2780/DDP) through down-regulation of ERK and up-regulation of p38 signaling pathways.
abstract: Cisplatin (CDDP) is a major chemotherapeutic drug used in the treatment of human ovarian cancer. Tubeimoside I (TBMS1) has also shown potent antitumor and antitumor-promoting effects, and may offer a promising new approach in the effective treatment of CDDP-resistant human ovarian cancers. This study aimed to investigate the effect of TBMS1 in sensitizing CDDP in CDDP-resistant human ovarian cancer cells (A2780/DDP). A variety of methods were employed to measure cell apoptosis, p38, ERK1/2 and glutathione S-transferase (GST)-π expressions. It was found that TBMS1 combined with CDDP promoted cell apoptosis, decreased proliferation activity and increased cytosolic Ca2+ levels. Bcl-2 protein expression was down-regulated but Bax was up-regulated. Moreover, GST-π mRNA and protein expression were decreased. TBMS1 reduced the resistance of the cells to CDDP-induced cytotoxicity. Both the p38 inhibitor (SB203580) and the ERK1/2 inhibitor (PD98059) effectively blocked this effect. These results suggest that TBMS1 can effectively sensitize CDDP in CDDP-resistant human ovarian cancer cells through the down-regulation of the ERK1/2 and the up-regulation of the p38 signaling pathways.
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Hai-Zhong
authors.initials: HZ
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yang
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: He
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Yin
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Li
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Liu
authors.forename: Ying-Xiong
authors.initials: YX
authors.lastname: Wang
mesh_terms: D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D012503:Saponins; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; C051084:tubeimoside I; D051549:Glutathione S-Transferase pi; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002945:Cisplatin; D002118:Calcium