Changes in intracellular redox status influence multidrug resistance in gastric adenocarcinoma cells

Tai,De-Jun; Jin,Wen-Sen; Wu,Cheng-Si; Si,Hong‑Wei; Cao,Xian‑Dong; Guo,Ai-Jun; Chang,Jia-Cong

doi:10.3892/etm.2012.591

Changes in intracellular redox status influence multidrug resistance in gastric adenocarcinoma cells

Authors:
- De-Jun Tai
- Wen-Sen Jin
- Cheng-Si Wu
- Hong‑Wei Si
- Xian‑Dong Cao
- Ai-Jun Guo
- Jia-Cong Chang
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Affiliations: Department of General Surgery, The First Affiliated Hospital, Anhui Medical University, Hefei 230032, P.R. China, Teaching and Research Section of Nuclear Medicine, Anhui Medical University, Hefei 230032, P.R. China, Department of Nuclear Medicine, The First Affiliated Hospital, Anhui Medical University, Hefei 230032, P.R. China
Published online on: May 24, 2012 https://doi.org/10.3892/etm.2012.591
Pages: 291-296

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Abstract

Multidrug resistance (MDR) to chemotherapeutic agents is a major obstacle for the treatment of various types of cancers. The exact mechanism of MDR has not yet been fully clarified, although it has been frequently associated with the variation of intracellular redox status. The levels of intracellular glutathione (GSH) are considered to play a vital role in the regulation of the intracellular redox status. In our study, we investigated the effects of buthionine sulfoximine (BSO), an inhibitor of GSH biosynthesis, and NAC, a cysteine source for GSH synthesis, on sensitive gastric adenocarcinoma cells (SGC7901) and cisplatin-resistant SGC7901/DDP cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The two cell lines were pretreated with various non-toxic concentrations of BSO for 24 h and combined with fluorouracil (5-FU) or mitomycin (MMC) in the presence or absence of NAC before culturing further. After various treatments, the IC50 values of MMC and 5-FU were calculated and intracellular GSH levels were measured using the glutathione reductase/5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) recycling assay without anticancer drug stimulation under the same microenvironments. The study demonstrated that BSO increased the sensitivity of the cells to chemotherapeutics while NAC exhibited the reverse effect, particularly in drug-resistant cells. It is, therefore, possible that changes in intracellular GSH levels affect the chemosensitivity of the resistant cells to a greater extent than that of their parent cells. This study indicates that variation in the intracellular redox status may be closely correlated with MDR and may provide a valuable basic strategy for anticancer therapy.

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