Effect and mechanism of Stellettin B induced human glioblastoma SF295 cells autophagy
10.3760/cma.j.issn.1673-4181.2018.02.004
- VernacularTitle:Stellettin B诱导人恶性胶质瘤SF295细胞发生自噬的作用及机理
- Author:
Chang ZHOU
1
,
2
;
Qian ZHANG
;
Xin PENG
;
Zhengming WANG
;
Yao LIU
;
Zhe ZHANG
;
Ran WANG
;
Dexin KONG
Author Information
1. 300070 天津医科大学药学院,天津市临床药物关键技术重点实验室
2. 300350 天津市海河医院药剂科
- Keywords:
Stellettin B;
Human glioblastoma;
Autophagy;
SF295 cell;
PI3K/Akt/mTOR pathway
- From:
International Journal of Biomedical Engineering
2018;41(2):125-130,147
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the autophagy of human glioblastoma SF295 cells induced by sponge-derived triterpenoid Stellittin B (Stel B) and to discuss the related mechanism. Methods The proliferation inhibitory activity of Stel B on SF295 cells was studied by WST-8 assay. The autophagy effect induced by Stel B on SF295 cells was evaluated bya variety of experimental techniques, including MDC staining, Western Blot assay, and mRFP-GFP-LC3 plasmid transfection method.The activity of Stel B on the representative signal proteins in PI3K/Akt/mTOR pathway in SF295 cells was examined by Western Blot. The anti-tumor activity of Stel B was detected by WST-8 assay after blocking autophagy by autophagy inhibitor chloroquine. Results Stel B could significantly inhibit the proliferation of SF295 cells with IC50 value as 0.026 μmol/L. Plenty of autophagosome was found in Stel B treated A549 cells by MDC staining. The expression of autophagy marker proteins including LC3B-II increased. The confocal microscopy results showed that Stel B promoted autophagosome forming and inhibitedthe fusion of autophagosome with lysosome. The Western Blot results showed that Stel B inhibited the expression of PI3K-p110 protein in SF295 cells and decreased the phosphorylation level of Akt and mTOR.The inhibitory effects of Stel B with different concentrations on SF295 cells were all enhanced by the inhibition of autophagy with chloroquine, and the differences were statistically significant (all P<0.05). Conclusion Stel B can induce SF295 cells autophagy via blocking PI3K/Akt/mTOR pathway. This autophagy effect is beneficial to the survival of SF295 cells. The antitumor activity of Stel B can be enhanced by a combination of autophagy inhibitors.
