SN50 enhances the effects of LY294002 on cell death induction in gastric cancer cell line SGC7901.

Abstract

INTRODUCTION:

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.

MATERIAL AND 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.

• Authors: Kui Zhao, Bao-Song Zhu, Wei Gong, Mo-Li Zhu, Zhi-Tao Gao, Yong-You Wu, Qiang Chen, Xiao-Dong Yang, Chun-Gen Xing
• Journal: Archives of medical science : AMS (Arch Med Sci) Vol. 9 Issue 6 Pg. 990-8 (Dec 30 2013) ISSN: 1734-1922 [Print] Poland
• PMID: 24482641 (Publication Type: Journal Article)