Nrf2 is a key factor in the reversal effect of curcumin on multidrug resistance in the HCT‑8/5‑Fu human colorectal cancer cell line

Nrf2 是姜黄素逆转 HCT‑8/5‑Fu 人结肠直肠癌细胞系多药耐药性的关键因素

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作者:Chao Zhang, Lian-Jun He, Hai-Zhu Ye, Ding-Feng Liu, Yi-Bao Zhu, Dong-Dong Miao, Sheng-Peng Zhang, Yun-Yu Chen, Yuan-Wei Jia, Jie Shen, Xiao-Ping Liu

Abstract

Multidrug resistance (MDR) is a major concern when using chemotherapy for the treatment of patients with colorectal cancer. MDR modulators are agents that can reverse MDR and, thus, enhance the chemosensitivity of tumor cells. The development of MDR modulators can improve the therapeutic efficacies of MDR in cancer. However, few effective MDR modulators have been identified so far. Curcumin has been reported to be an effective compound in the reversal of MDR in colorectal cancer cells. However, the mechanisms associated with the reversal effect of curcumin on MDR and its regulation of target factors in MDR cells remain to be fully elucidated. 3‑(4,5‑dimethyl‑2‑thiazol)‑2,5‑diphenyltetrazolium bromide assays, flow cytometer apoptosis assays as well as mRNA and protein expression assays were performed in the present study, and the results confirmed the reversal effect of curcumin on HCT‑8/5‑Fu cells and provided evidence that activated nuclear factor erythroid 2‑related factor (Nrf2) deficiency induced by the curcumin altered the B‑cell lymphoma 2 (Bcl‑2) associated X protein/Bcl‑2 expression ratio, which led to the induction of apoptosis in HCT‑8/5‑Fu cells. These results indicated that Nrf2 may have a functional in the reversal effect of curcumin and contribute, at least in part, to the outcomes of chemotherapy in patients with MDR.

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