抑制肾癌细胞自噬可增强癌细胞对舒尼替尼的敏感性

发布时间：2018-05-18 00:44

本文选题：自噬 + 肾癌　；参考：《细胞与分子免疫学杂志》2017年03期

【摘要】：目的检测肾癌中自噬的表达水平及其对舒尼替尼耐药性的影响。方法采用免疫组织化学法检测自噬相关基因5(ATG5)与微管相关蛋白1轻链3(LC3)在99例肾透明细胞癌组织中的表达,并进行临床病理及生存分析;通过慢病毒感染技术构建ATG5低表达的A-498肾癌细胞株,Western blot法检测干扰效果;流式细胞术检测ATG5正常表达与低表达的A-498细胞增殖的变化;经舒尼替尼刺激后,MTT法检测A-498细胞存活率。结果 ATG5与LC3在肾癌组织中的表达显著高于癌旁组织,且ATG5与LC3的表达与肾癌的分型、分化程度、TNM分期、术后生存率具有相关性,而与性别、年龄、部位、大小无关;与对照组相比,ATG5低表达的A-498细胞ATG5与LC3蛋白表达明显降低、细胞增殖率(G2/M期百分比)明显降低;且对舒尼替尼敏感性增加,与舒尼替尼呈剂量依赖性。结论肾癌组织中自噬活跃,抑制自噬ATG5表达后,明显增强人肾癌细胞对舒尼替尼的敏感性。
[Abstract]:Objective to detect the expression of autophagy in renal cell carcinoma (RCC) and its effect on sulnitinib resistance. Methods Immunohistochemical method was used to detect the expression of autophagy associated gene 5 (ATG5) and microtubule-associated protein 1 light chain 3LC3 in 99 cases of renal clear cell carcinoma (RCC). The cell line A-498 with low expression of ATG5 was constructed by lentivirus infection. The interference effect was detected by Western blot assay, the normal expression of ATG5 and the proliferation of low expression A-498 cells were detected by flow cytometry, and the survival rate of A-498 cells was detected by MTT method after stimulation by sunitinib. Results the expression of ATG5 and LC3 in renal cell carcinoma was significantly higher than that in paracancerous tissue. The expression of ATG5 and LC3 was correlated with the classification of renal cell carcinoma, the differentiation degree of renal carcinoma and the survival rate after operation, but not with sex, age, location and size. Compared with the control group, the expression of ATG5 and LC3 protein in A-498 cells with low ATG5 expression was significantly decreased, and the cell proliferation rate was significantly lower than that in the control group, and the sensitivity to sunitinib was increased in a dose-dependent manner. Conclusion autophagy is active in renal cell carcinoma, and inhibition of autophagy ATG5 expression can significantly enhance the sensitivity of human renal cell carcinoma to sunitinib.
【作者单位】：第三军医大学第一附属医院肾科;第三军医大学药物研究所;
【基金】：国家自然科学基金(81370846)
【分类号】：R737.11

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