期刊
MOLECULAR MEDICINE REPORTS
卷 4, 期 5, 页码 985-992出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2011.513
关键词
tubeimoside I; cisplatin; ovarian cancer; signaling pathway
资金
- National Natural Science Foundation of China [30973169]
- Natural Science Foundation of Chongqing [CSTC-2009BA5083]
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)-pi expressions. It was found that TBMS1 combined with CDDP promoted cell apoptosis, decreased proliferation activity and increased cytosolic Ca2+ levels. BcI-2 protein expression was down-regulated but Bax was up-regulated. Moreover, GST-pi 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.
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