姜黄素通过对miR-409-3p的作用调控ERCC1表达并增强耐药结直肠癌细胞对奥沙利铂的敏感性。
Curcumin Regulates ERCC1 Expression and Enhances Oxaliplatin Sensitivity in Resistant Colorectal Cancer Cells through Its Effects on miR-409-3p.
作者信息
Han Wei, Yin Hongli, Ma Hao, Wang Yi, Kong Desong, Fan Zhimin
机构信息
Chinese Medicine Modernization and Big Data Research Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210022, China.
General Surgery Department, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210022, China.
出版信息
Evid Based Complement Alternat Med. 2020 Sep 17;2020:8394574. doi: 10.1155/2020/8394574. eCollection 2020.
BACKGROUND
Oxaliplatin (L-OHP) resistance is a major obstacle to the effective treatment of colorectal cancer. The resistance mechanism(s) of colorectal tumors to L-OHP may be related to the regulation of by cancer-expressed miRNAs, but no in-depth studies on the miRNAs that affect drug resistance have been performed. Curcumin (Cur) can reverse the drug resistance of cancer cells, but its effects on ERCC1 expression and miRNA profiles in colorectal cancer have not been studied.
METHODS
To study the regulation effect of curcumin on ERCC1 expression and its effects on miRNAs, the L-OHP-resistant colorectal cancer cell line HCT116/L-OHP was established. MTT assays were used to evaluate cell proliferation. Flow cytometry was used to investigate apoptotic induction. Western blot and RT-PCR analysis were used to evaluate the expression of drug-associated ERCC1, Bcl-2, GST-, MRP, P-gp, and survivin.
RESULTS
HCT116//L-OHP cell lines were successfully established. The combination of L-OHP and curcumin could reduce L-OHP resistance . In addition, combination therapy inhibited the expression of ERCC1, Bcl-2, GST-, MRP, P-gp, and survivin at the mRNA and protein level. Curcumin was found to inhibit ERCC1 through its ability to modulate miR-409-3p.
CONCLUSION
Curcumin can overcome L-OHP resistance in colorectal cancer cells through its effects on miR-409-3p mediated ERCC1 expression.
背景
奥沙利铂（L-OHP）耐药是有效治疗结直肠癌的主要障碍。结直肠肿瘤对L-OHP的耐药机制可能与癌症表达的微小RNA（miRNA）的调控有关，但尚未对影响耐药性的miRNA进行深入研究。姜黄素（Cur）可逆转癌细胞的耐药性，但其对结直肠癌中ERCC1表达和miRNA谱的影响尚未得到研究。
方法
为研究姜黄素对ERCC1表达的调控作用及其对miRNA的影响，建立了L-OHP耐药的结直肠癌细胞系HCT116/L-OHP。采用MTT法评估细胞增殖。流式细胞术用于研究细胞凋亡诱导情况。蛋白质免疫印迹法和逆转录-聚合酶链反应（RT-PCR）分析用于评估与药物相关的ERCC1、Bcl-2、谷胱甘肽S-转移酶（GST-）、多药耐药相关蛋白（MRP）、P-糖蛋白（P-gp）和生存素的表达。
结果
成功建立了HCT116//L-OHP细胞系。L-OHP与姜黄素联合使用可降低L-OHP耐药性。此外，联合治疗在mRNA和蛋白质水平上抑制了ERCC1、Bcl-2、GST-、MRP、P-gp和生存素的表达。发现姜黄素通过调节miR-409-3p抑制ERCC1。
结论
姜黄素可通过其对miR-409-3p介导的ERCC1表达的影响克服结直肠癌细胞中的L-OHP耐药性。
Zotero 插件