SN50 enhances the effects of LY294002 on cell death induction in gastric cancer cell line SGC7901.
BACKGROUND
In the previous study, we found that the inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 induced SGC7901 cell death in vitro. We did not know whether SN50, which is a specific inhibitor of nuclear factor κB (NF-κB), could increase the cell death induction of gastric cancer of LY294002 in vitro, and we also wanted to know the mechanism of it, which might be applied to clinical tumor therapy.


METHODS
The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cytotoxic effects of the drugs. Mitochondrial membrane potential was measured using the fluorescent probe JC-1. Hoechst 33258 staining was used to detect apoptosis and necrosis morphological changes after LY294002 and/or SN50 treatment. Expression of p53, PUMA and Beclin1 were determined with real-time polymerase chain reaction (RT-PCR) analysis. We used transmission electron microscopy to identify ultrastructural changes in SGC7901 cells after LY294002 and/or SN50 treatment.


RESULTS
In this study, we found that treating the human gastric cancer cells SGC7901 with SN50 could significantly enhance the effects of LY294002 on inducing cell death after 24 h, compared to the control group (p < 0.05). Detection of mitochondrial potential and transmission electron microscopic examination indicated that the rate of cell death increased progressively. The expression of p53, PUMA and Beclin1 was up-regulated.


CONCLUSIONS
The NF-κB inhibitor SN50 could enhance the role of LY294002 on inducing cell death of human gastric cancer cells SGC7901, which might be a promising new approach to gastric cancer therapy.
Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou, China.
Kui
K
Zhao
Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou, China.
Bao-Song
BS
Zhu
Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou, China.
Wei
W
Gong
Pharmacy College, Xinxiang Medical University, Xinxiang Henan, China.
Mo-Li
ML
Zhu
Immunologic Research Center of Xinxiang Medical University, Xinxiang Henan, China.
Zhi-Tao
ZT
Gao
Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou, China.
Yong-You
YY
Wu
Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou, China.
Qiang
Q
Chen
Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou, China.
Xiao-Dong
XD
Yang
Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou, China.
Chun-Gen
CG
Xing
cell death; gastric cancer; nuclear factor κB; phosphatidylinositol 3-kinase