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Research articles

ScienceAsia 49 (2023):ID 320-327 |doi: 10.2306/scienceasia1513-1874.2023.015

Genistein potentiates TRAIL-induced apoptosis in MGC-803 human gastric cell lines by downregulation of Akt pathway and improvement of Bax/Bcl-2 ratio

Xingguo Wanga,†, Ping Yaob,†, Guojin Gongc, Xuting Zhangd,*

ABSTRACT:      Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as an anti-cancer drug induces robust apoptosis in tumor cells, various human gastric cancer cells have shown resistance to TRAIL-induced apoptosis. Herein, we evaluated the therapeutic effects of a combination therapy with flavonoid genistein and TRAIL in gastric cancer cell line MGC-803 to overcome their resistance to TRAIL-induced apoptosis. MGC-803 cells were treated with various concentrations of genistein (0?160 ?M) to determine IC50 values using tetrazolium-based MTT assay. The apoptosis percentages were measured using Annexin-V/PI and fluorescence-activated cell sorting (FACS) analysis in cells treated with high-dose TRAIL (100 ng/ml) alone or in combination with low-dose genistein (20 ?M). The expression levels of candidate genes, Akt, anti-apoptotic protein Bcl-2, pro-apoptotic protein Bax, as well as death receptors (DRs) 4 and 5, were assessed at mRNA levels via Real-Time PCR and protein levels through western blotting in MGC-803 cells. The 72.7?3.07 ?M concentration was estimated as IC50 value for genistein in MGC-803 cells at 24 h of treatment. Also, the combination therapy with low-dose genistein significantly improved apoptosis percentages in MGC-803 cells compared with high-dose TRAIL-treated cells and control cells. The combination therapy led to the upregulation of DR5 and Bax expression with no significant effect on DR4 expression. Further, TRAIL plus genistein attenuated the expression of Akt, and Bcl-2, culminating in apoptosis. The obtained results indicated that genistein could potentiate apoptosis in MGC-803 cells when combined with TRAIL through upregulation of DR5 expression and downregulation of survival-involved Akt signaling axis concomitant with improving the Bax/Bcl-2 ratio.

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a Department of General Surgery, Yulin NO. 2 Hospital, Yulin, Shaanxi 719000 China
b Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006 China
c Department of General Surgery, Xichang People?s Hospital, Xichang, Sichuan 615000 China
d Department of Rehabilitation Medicine, Zhuji People?s Hospital of Zhejiang Province, Zhuji, Zhejiang 311800 China

* Corresponding author, E-mail: xuting.zhang2000@gmail.com

Received 6 Apr 2022, Accepted 24 Sep 2022