靶向抑制miR-155增加骨髓瘤细胞对化疗药物的敏感性  

Targeted inhibition of miR-155 increases the sensitivity of myeloma cells to chemotherapeutic drugs

作　　者：李岚 高瑛[1] 郑研 张维华[1,2] 苗玉迪[1] LI Lan;GAO Ying;ZHENG Yan;ZHANG Weihua;MIAO Yudi(Department of Hematology,Shaanxi Provincial People's Hospital,Shaanxi Xi'an 710068,China;Central Laboratory,Shaanxi Provincial People's Hospital,Shaanxi Xi'an 710068,China)

机构地区：[1]陕西省人民医院血液内科,陕西西安710068 [2]陕西省人民医院中心实验室,陕西西安710068

出　　处：《现代肿瘤医学》2021年第4期548-552,共5页Journal of Modern Oncology

基　　金：陕西省社会发展科技攻关项目(编号:2015SF065);陕西省自然科学研究项目(编号:18PJ096)。

摘　　要：目的:探讨靶向抑制miR-155对骨髓瘤细胞化疗敏感性的影响,并研究其分子作用机制。方法:利用qRT-PCR测定人骨髓瘤细胞株及耐药株中miR-155的表达水平;利用Lipofectamine~(TM) 2000将miR-155 inhibitor和阴性对照转染至人骨髓瘤耐药细胞株中;利用MTT法检测转染后人骨髓瘤耐药细胞对化疗药物的敏感性和增殖活性;利用Western-blot实验测定转染后人骨髓瘤耐药细胞中E-cadherin蛋白的表达量。结果:qRT-PCR实验结果显示,人骨髓瘤耐药细胞中miR-155的表达水平较人骨髓瘤细胞显著上调(P<0.001);MTT实验结果显示,转染miR-155 inhibitor抑制miR-155的表达,人骨髓瘤耐药细胞对化疗药物的敏感性显著增加(P<0.05),细胞增殖活性显著降低(P<0.05);Western-blot实验结果显示,人骨髓瘤耐药细胞中E-cadherin蛋白的表达量显著增加(P<0.01)。结论:通过靶向抑制miR-155的表达可以增加骨髓瘤细胞对化疗药物的敏感性,其机制可能与上皮间质转化(EMT)生成的逆转有关。Objective:To investigate the effect of targeted inhibition of miR-155 on chemotherapy sensitivity of myeloma cells and its molecular mechanism.Methods:The expression of miR-155 in myeloma cell line and drug resistant line was measured by qRT-PCR.Lipofectamine TM 2000 was used to transfer miR-155 inhibitor and negative control into human myeloma resistant cell line.MTT assay was used to detect the sensitivity to chemotherapeutic drugs and proliferative activity after transfection of human myeloma drug-resistant cells.The expression of E-cadherin protein in human myeloma drug-resistant cells after transfection was determined by Western-blot assay.Results:The result of qRT-PCR showed that the expression level of miR-155 in human myeloma drug-resistant cells was significantly higher than that of human myeloma cells(P<0.001).The results of MTT showed that the expression of miR-155 was inhibited by the transfection of miR-155 inhibitor.The sensitivity of human myeloma drug-resistant cells to chemotherapy drugs was significantly increased(P<0.05).The cell proliferation activity was significantly decreased(P<0.05).The result of Western-blot showed that the expression of E-cadherin protein in human myeloma-resistant cells increased significantly(P<0.01).Conclusion:Targeted inhibition of miR-155 expression can increase the sensitivity of myeloma cells to chemotherapeutic drugs,and the mechanism may be related to the reversal of epithelial mesenchymal transition(EMT)emergence.

关 键 词：MIR-155 骨髓瘤 耐药 E-CADHERIN蛋白 

分 类 号：R733.3[医药卫生—肿瘤]