Enhancing effect of gambogic acid on the sensibility of human gastric carcinoma SGC7901/DDP cells to cisplatin

doi:10.16098/j.issn.0529-1356.2018.03.011

Abstract

Abstract:

Objective The aim of this study is to investigate the effect of gambogic acid (GA) on the sensibility of human gastric carcinoma SGC7901/DDP cells to cisplatin (DDP) and its possible mechanism. Methods The drug-resistant SGC7901/DDP cells were established by stepwise exposure to DDP. CCK-8 assay was employed to detect the cytotoxic effect of GA and DDP on SGC7901/DDP cells, and the combined effect of GA and DDP was analyzed by Chou-Talalay method . The cell apoptosis was studied by flow cytometry. Western blotting was performed to detect the protein levels of Bcl-2, Bax, Survivin, multidrug resistance-associated protein 2 (MRP2), phosphorylated c-Jun N-terminal kinase (p-JNK) (Thr183/Tyr185) and JNK. Results The IC₅₀ values of GA and DDP were 2.94 μmol/L and 39.76 μmol/L after 48 hours treatment respectively, and the combined both drugs improved the antitumor effects on SGC7901/DDP cells. GA enhanced cisplatin-induced apoptosis (P<0.05), down-regulated Survivin and MRP2 and up-regulated Bax at the protein level (P<0.05), and inhibited phosphorylation of JNK in SGC7901/DDP cells (P<0.05). SP600125, a specific inhibitor of JNK, declined the protein level of MRP2 (P<0.05). Conclusion GA may enhance the sensibility of SGC7901/DDP cells to cisplatin by down-regulating MRP2 as a result of inactivation of the JNK signaling pathway, and up-regulating Bax and down-regulating Survivin.

Key words: Gambogic acid, Gastric carcinoma, Cisplatin, Drug resistance, SGC7901/DDP cell, Western blotting, Human

TONG Lei WANG Li-jun YUAN Lei. Enhancing effect of gambogic acid on the sensibility of human gastric carcinoma SGC7901/DDP cells to cisplatin[J]. Acta Anatomica Sinica, 2018, 49(3): 337-341.

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