关键词: 姜黄素, 胃肿瘤, 磷脂酰肌醇3-激酶, 蛋白激酶B, 哺乳动物雷帕霉素靶蛋白, 细胞增殖, 细胞侵袭, 细胞凋亡

Abstract:

Objective To observe the effect of curcumin on proliferation and invasion of the gastric cancer MGC-803 cells in vitro and in vivo， and to discuss the mechanism of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian rapamycin target protein （mTOR） signaling pathway. Methods The gastric cancer MGC-803 cells were divided into control group， low dose （10 μmol·L^－1） of curcumin group， middle dose （20 μmol·L^－1） of curcumin group，and high dose （40 μmol·L^－1） of curcumin group. The proliferation abilities of the MGC-803 cells in various groups were detected by CCK-8 method；the invasion abilities of the MGC-803 cells in various groups were detected by Transwell method；the apoptotic rates of the MGC-803 cells were detected by flow cytometry. The MGC-803 cells were used to establish the gastric cancer transplanted tumor model and the mice were treated with low（0.5 mg·kg^－1）， middle （1.0 mg·kg^－1），and high （2.0 mg·kg^－1） doses of curcumin， and the inhibitory effect of curcumin on the tumor growth of the mice in various groups was observed. TUNEL method was used to detect the apoptosis of the tumor cells in transplanted tumor tissue of the mice in various groups；the expression levels of PI3K-Akt-mTOR signaling pathway proteins in transplacted tumor tissue of the mice in various groups were detected by Western blotting ththod. Results Compared with control group， the proliferation abilities and number of invasion cells in different doses of curcumin groups were significantly decreased （P<0.05）， and the apoptotic rates were significantly increased （P<0.05）； the cell proliferation ability and the number of invasion cells in low dose of curcumin group were significantly higher than those in high dose of curcumin group （P<0.05）， and the apoptotic rate was significantly lower than that in high dose of curcumin group （P<0.05）.Compared with control group， the volumes of transplanted tumor of the mice in different doses of curcumin groups were significantly decreased （P<0.05）.The apoptotic rate of the cells in transplanted tumor tissue of the mice in control group was low， and the apoptotic rate of the cells in transplated tumor tissue of the mice in middle dose of curcumin group was significantly higher than that in low dose of curcumin group （P<0.05）， while the apoptotic rate of the cells in transplated tumor tissue of the mice in high dose of curcumin group was significantly higher than that in middle dose of curcumin group （P<0.05）. Compared with control group， the proteins expression levels of PI3K， phosphorylated Akt（p-Akt） and phosphorylated mTOR（p-mTOR） in transplanted tumor tissue of the mice in different doses of curcumin groups were significantly decreased （P<0.05）；the expression levels of PI3K， p-Akt， and p-mTOR proteins in transplanted tumor tissue of the mice in low dose of curcumin group were significantly lower than those in middle dose of curcumin group （P<0.05）； the expression levels of PI3K， p-Akt， and p-mTOR proteins in transplanted tumor tissue of the mice in high dose of curcumin group were significantly lower than those in middle dose of curcumin group （P<0.05）. Conclusion Curcumin can effectively inhibit the proliferation of tumor， decrease the invasion ability， and increase the apoptotic rate of the tumor cells；its mechanism may be related to down-regulation of expressions of PI3K/Akt/mTOR signaling pathway proteins.

Key words: Curcumin, Stomach neoplasm, Phosphatidylinositol 3-kinase, Protein kinase B, Mammalian target protein of rapamycin, Cell proliferation, Cell invasion, Apoptosis