Department of Nutrition, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China.
Second Clinical College of Zhejiang Chinese Medical University, No.548 Binwen Road, Binjiang District, Hangzhou, Zhejiang Province.
Biomed Pharmacother. 2020 Sep;129:110381. doi: 10.1016/j.biopha.2020.110381. Epub 2020 Jul 4.
Colorectal cancer is a kind of gastrointestinal tumor with rising morbidity and mortality. 5-fluorouracil is one of the most effective chemotherapy drugs for the treatment of CRC. However, clinical data reported dramatic resistance on the treatment for CRC with 5-fluorouracil. Present study aims to explore the anti-resistant effect of curcumin and its mechanism.
MTT assay was used to evaluate the proliferation of rHCT-116 cells. Flow cytometry was used to determine the apoptosis and cell cycle of rHCT-116 cells. Western Blot was performed to detect the expression level of TET1, NKD2, E-cadherin, Vimentin, β-catenin, TCF4 and Axin in transfected rHCT-116 cells.
5-fluorouracil resistant HCT-116 cells were successfully established. Curcumin was found to be effective in the inhibition of proliferation, inducement of apoptosis and block of G0/G1 phase on 5-fluorouracil treated HCT-116 cells. The expression of TET1 and NKD2 was greatly inhibited by high dosage of curcumin. The WNT signal pathway and EMT progress were suppressed in rHCT-116 cells by high dosage of curcumin. The inhibitory effects of curcumin on WNT signal pathway and EMT progress were verified to be consistent with Pax-6, TET1 and NKD2.
Curcumin might exert anti-resistant effect of 5-FU on HCT-116 cells by regulating the TET1-NKD2-WNT signal pathway to inhibit the EMT progress.
结直肠癌是一种发病率和死亡率不断上升的胃肠道肿瘤。5-氟尿嘧啶是治疗 CRC 最有效的化疗药物之一。然而，临床数据报道 5-氟尿嘧啶治疗 CRC 时存在明显的耐药性。本研究旨在探讨姜黄素的抗耐药作用及其机制。
MTT 法评估 rHCT-116 细胞的增殖情况。流式细胞术检测 rHCT-116 细胞的凋亡和细胞周期。Western Blot 检测转染 rHCT-116 细胞中 TET1、NKD2、E-cadherin、Vimentin、β-catenin、TCF4 和 Axin 的表达水平。
成功建立了 5-氟尿嘧啶耐药 HCT-116 细胞。发现姜黄素可有效抑制 5-氟尿嘧啶处理的 HCT-116 细胞的增殖，诱导凋亡，并阻断 G0/G1 期。高剂量姜黄素可显著抑制 TET1 和 NKD2 的表达。高剂量姜黄素抑制 rHCT-116 细胞中的 WNT 信号通路和 EMT 进展。高剂量姜黄素对 WNT 信号通路和 EMT 进展的抑制作用与 Pax-6、TET1 和 NKD2 一致。
姜黄素可能通过调节 TET1-NKD2-WNT 信号通路抑制 EMT 进展，发挥对 HCT-116 细胞 5-FU 的抗耐药作用。
