Diallyl disulfide augments sensitivity of DJ-1 overexpressed human gastric cells to 5-FU

Yi XUN; Hong XIA; Zhi-Min LI; Fang LIU; Qi SU; Bo SU; Yi XUN; Zhi-Min LI; Bo SU

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Diallyl disulfide augments sensitivity of DJ-1 overexpressed human gastric cells to 5-FU

Author: Yi XUN ¹ ; Hong XIA ¹ ; Zhi-Min LI ¹ ; Fang LIU ¹ ; Qi SU ¹ ; Bo SU ¹ ; Yi XUN ² ; Zhi-Min LI ² ; Bo SU ³
Author Information

1. Cancer Research Institute, Key Laboratory of Cancer Cellular and Molecular Pathology, Hunan Provincial University, Hengyang Medical School, University of South China
2. Center for Gastric Cancer Research of Hunan Province, Dept of Oncology, First Affiliated Hospital, University of South China
3. Institute of Pharmacy and Pharmacology, School of Pharmacy, Hengyang Medical School, University of South China
Publication Type:Journal Article
Keywords: 5-fluorouracil; diallyl disulfide; DJ-1; drug resistance; gastric cancer cells; P-glycoprotein
From: Chinese Pharmacological Bulletin 2024;40(1):99-105
CountryChina
Language:Chinese
Abstract: Aim To investigate whether diallyl disul-fide (DADS) augments the sensitivity of DJ-1 (protein/ nucleic acid deglycase) overexpressed human gastric SGC7901 cells to 5-FU (5-fluorouracil). Methods The experimental groups include control group, DADS group, VCR (vincristine) group, VCR + DADS group, DJ-1 group, DJ-1 + DADS group. MTT was used to analyze the effect of DADS on 5 -FU (5 -fluorou- racil) induced proliferation inhibition. Flow cytometry was performed to examine the effect of DADS on cell apoptosis. RT-PCR, Western blot, and immunofluo-rescence were used for determine the effect of DADS on the drug resistance associated gene expression. Results DADS enhanced the proliferation inhibitory effect of 5-FU on DJ-1 overexpressed cells and VCR resistant cells. DADS could induce apoptosis in VCR-resistant cells. DADS downregulated the expression of DJ-1 while inducing apoptosis in DJ-1 overexpressed cells. DJ-1 overexpression upregulated the expression of P-gp (P-glycoprotein), Bcl-2, and XIAP (X-linked inhibitor of apoptosis protein), downregulated the expression of caspase-3. DADS decreased the expression of P-gp, Bcl-2, and XIAP, while increased the expression of caspase-3 in DJ-1 overexpressed cells and VCR-resistant cells. Conclusions DADS can augment the sensitivity of DJ-1 overexpressed cells to 5-FU, which is related to its antagonism against DJ-1 mediated upregula- tion of P-gp, Bcl-2, XIAP, and downregulation of caspase-3.