IL-6诱导卵巢癌细胞对他莫西芬产生耐药的实验研究

IL-6 induces ovarian cancer cell resistance to tamoxifen

目的:研究IL-6在诱导卵巢癌细胞对他莫西芬(TAM)产生耐药中的作用。方法:选择A2780(不分泌IL-6,但表达其受体,且对TAM敏感)和CAOV3(高表达IL-6及其受体,且对TAM耐药)细胞作为研究模型,应用重组IL-6短期处理或将ss/as IL-6基因稳定转染至A2780(该数据已有文章发表)及CAOV3细胞,通过MTT、RT-PCR、ELISA等观察内源性及外源性IL-6是否影响卵巢癌细胞对TAM的敏感性。结果:经稳定转染得到IL-6中、高抑制表达的2个CAOV3/asIL-6细胞克隆,与空载体转染细胞CAOV3/pcDNA3.1+相比,IL-6分泌水平分别下降了63.82%和75.69%(P<0.05),其IL-6 mRNA水平与其分泌水平相似;外源性IL-6处理及内源性过表达IL-6均可诱导A2780细胞对TAM产生耐药,而内源性抑制IL-6表达则可恢复CAOV3细胞对TAM的敏感性。结论:IL-6可诱导卵巢癌细胞对TAM产生耐药,IL-6有可能是卵巢癌抗雌激素治疗耐药中的重要一环,有望成为逆转卵巢癌抗雌激素治疗耐药的重要靶点。

Objective: To explore the effect of tamoxifen resistance caused by exogenous and endogenous IL-6 in ovarian cancer cells. Methods: A2780 and CAOV3 cells were used as research models;we retreated with exogenous IL-6 to obtain A2780/preIL-6 cells. The antisense IL-6 gene was stably transfected into CAOV3 cells, and the IL-6 mRNA and IL-6 secretion levels of stably transfected cells were detected by RT-PCR and ELISA. Ovarian cancer cell activity was measured by MTT assay. Results: CAOV3/asIL-6 with different IL-6 secretion levels were stably transfected, and their IL-6 secretion levels were decreased by 63.82% and 75.69%, respectively, compared with their untransfected cells CAOV3(P<0.05), and its IL-6 mRNA level was consistent with its secretion level;Exogenous IL-6, endogenous overexpression of IL-6 induced resistance to tamoxifen in A2780 cells, whereas inhibition of IL-6 expression restored the sensitivity of CAOV3 cells to tamoxifen. Conclusion: IL-6 can induce tamoxifen resistance in ovarian cancer cells. IL-6 may be an important part of anti-estrogen resistance in ovarian cancer, and it is expected to be an important factor in reversing the anti-estrogen resistance of ovarian cancer.