Trichostatin A inhibits the proliferation of gastric cancer cells through the promotion of autophagy via p-Akt/p-mTOR pathway
10.16571/j.cnki.1008-8199.2020.01.002
- VernacularTitle: 曲古抑菌素A抑制胃癌细胞增殖的分子机制
- Author:
Zhi-ming TANG
1
;
Chun-ming GU
1
;
Yang LIU
1
;
Wei-ning QIN
1
;
Jia-li LI
1
;
Ping YANG
1
;
Fang-hong YANG
1
;
Yun-li CAI
1
;
Fu-yun WU
1
;
Shan LI
1
Author Information
1. Institute of Basic Medical Science, Hubei University of Medicine, Shiyan 422000,Hubei,China
- Publication Type:Journal Article
- Keywords:
trichostatin;
protein kinase B;
autophagy;
proliferation
- From:
Journal of Medical Postgraduates
2020;33(1):7-11
- CountryChina
- Language:Chinese
-
Abstract:
Objective Trihostatin A (TSA) is a histone deacetylase inhibitor of oxime salts, which has certain anti-tumor activity. This article mainly investigates the molecular mechanism of TSA inhibiting cell proliferation through p-AKT/p-mTOR pathway in gastric cancer cells. Methods Gastric cancer cell line-SGC-7901 were treated with TSA of different concentrations, and the inhibition rate of TSA on the cells was detected by MTT assay. The cells were divided into control group (without any treatment), TSA-treated group (200ng/ml TSA), p-AKT covering group (200 ng/mL TSA+8 μg/mL SC79) and autophagy inhibition group (5 mmol/mL 3-methyladenine+200 ng/mL TSA). The protein expression distribution of Lc3 in control and TSA group were detected by cell immunofluorescence staining. The relative expression levels of p-AKT, p-mTOR and autophagy related proteins Lc3 and P62 in control group, TSA group and p-AKT covering group were detected by Western blot. The proliferation of cells in control group, TSA group, p-AKT covering group and autophagy inhibition group were measured by EdU and cell count assay. Results After 24h of treatment, Lc3 in TSA group formed a large number of granular aggregates in the cytoplasm, and the fluorescence distribution changed from the initial diffuse to dense. The TSA group showed a significant reduction in green fluorescence compared with the control group in the EdU experiment. The expression levels of p-AKT in the control group, TSA group and the autophagy inhibition group were 1.78±0.19, 0.92±0.03 and 1.71±0.19, respectively, and Lc3 were 0.21±0.01, 0.79±0.06 and 0.55±0.10, respectively. Compared with the control group, the relative expression level of p-AKT in the TSA group all decreased, while the expression level of Lc3 increased (P <0.05). p-mTOR in the three groups was 0.80±0.16, 0.45±0.04 and 0.98±0.16, respectively. Compared with the control group, the relative expression level of p-mTOR in the TSA group all decreased (P <0.05). P62 in the three groups was 1.17±0.15, 0.48±0.08 and 0.77±0.10, respectively. Compared with the control group, the relative expression level of P62 in the TSA group all decreased (P<0.05). Compared with the TSA group, p-AKT, p-mTOR and P62 expression in the p-AKT covering group increased (P<0.05), while Lc3 expression decreased (P<0.05). Compared with the control group, the inhibition effect of cell growth curve was the most obvious in the TSA group, while the cell growth curve of p-AKT covering group and autophagy inhibition group showed a partial recovery compared with the TSA group. Conclusion TSA can promote autophagy by inhibiting p-AKt/p-mTOR pathway, thus inhibiting the proliferation of gastric cancer cells.
