Effects and mechanism of Annexin A11 on human gastric cancer cell line SGC7901 drug resistance to fluorouracil

Objective To investigate the effect of Annexin A11 (ANXA11) on 5-fluorouracil (5-Fu) resistance of human gastric cancer cell line SGC7901. Methods The expression of ANXA11 in human gastric cancer cell lines SCG7901 and BGC823 was detected. ANXA11-small interfering RNA (siRNA) and negative control sequences were transiently transfected into SGC7901 cells. cell counting kit-8 (CCK-8) assay was used to detect the sensitivity to 5-Fu with different dose (1, 10, 20, 40, 80 μg/ml) in each group. Apoptosis rate of each group was detected by flow cytometry. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to detect the changes of B cell lymphoma/leukemia-2 associated X protein (bax), B cell lymphoma/leukemia-2 (bcl-2) and TS. Results Compared with the BGC-823 cells, ANXA11 mRNA and protein expressions in SGC7901 cells were significantly higher (t=3.212, P=0.033; t=-10.768, P=0.000). 50% inhibitory dose (IC50) and 20% inhibitory dose (IC20) of the transfection group (transfected with ANXA11-siRNA) was significantly lower than the negative control (transfected with NS-siRNA) and blank control group (F=47.500, P=0.000; F=45.523, P=0.000). The apoptosis rate increased significantly in the transfection and the combined group (transfected with ANXA11-siRNA and combined with IC20 concentration of 5-Fu) compared with the negative control and the blank control group (F=117.525, P=0.000), and the apoptosis rate of the combined group was significantly higher than that of the transfection group (P<0.05). The expression of ANXA11 protein decreased significantly in the transfection and the combined group (F=118.403, P=0.000). Compared with the negative control group and the blank control group, the expression of bax in the transfection group and the combined group were up-regulated (F=35.608, P=0.000), while those of bcl-2 and TS were significantly down-regulated (F=30.048, P=0.000; F=22.874, P=0.000). Conclusion Suppression of ANXA11 expression can improve the sensitivity of human gastric cancer cell line SGC7901 to 5-Fu, which may be related to the down-regulation of TS, bcl-2 and up-regulation of bax expression. Key words: Annexin A11; Gastric cancer; 5-Fluorouracil; Chemotherapy resistance; RNA interference technique