Shugoshin1在非小细胞肺癌多西紫杉醇耐药中的作用

High expression of Shugoshin1 induced taxotere resistance in NSCLC

目的:探讨Shugoshin1在非小细胞肺癌A549细胞对多西紫杉醇耐药中的作用。方法:用Western-blot及RT-PCR检测Sgo1在非小细胞肺癌紫杉醇耐药细胞株A549/Taxotere及亲本A549中的表达差异。通过构建Sgo1的si-RNA质粒和过表达质粒经慢病毒包装分别转染A549/Taxotere及亲本A549细胞,利用Western-blot及RT-qPCR鉴定其干预效果。MTT比色法比较下调及上调Sgo1的表达后细胞对化疗药物多西紫杉醇敏感性的影响。结果:在非小细胞肺癌多西紫杉醇耐药细胞株中,Sgo1的表达明显高于其亲本细胞株A549。通过外源性筛选和鉴定,经慢病毒包装载体,成功构建了Sgo1表达上调和下调的细胞株;MTT试验发现:抑制Sgo1的表达能显著增加A549/Taxotere对多西紫杉醇的敏感性,而外源性上调Sgo1的表达能明显降低A549对多西紫杉醇的敏感性。结论:Sgo1的表达与非小细胞肺癌细胞株A549紫杉醇耐药性密切相关。

Objective：To explore the role of Sgol in taxotere drug resistance in NSCLC A549. Methods：By semi-quantitative RT- PCR and Western -blot, the expression of Sgol in .4549 and A549/Taxotere was measured. A lentivirus vector was successfully constructed to suppress the expression of Sgol in A549/Taxotere while another lentivirus vector was built to increase the expression of Sgol in A549, MTT assay was used to determine the docetaxel sensitivity between A549/Taxotere with decreased expression of Sgol and A549/Taxotere as well as between A549 with upregulation of Sgol and .4549. Results： Semiquantitative RT - PCR and Western - blot showed that Sgol was highly expressed in A549/Taxotere than in A549 ; MTT assay showed that the ICso of A549/Taxotere and A549/Taxotere intro- ducing Sgol si -RNA lentivirus vector were 4168.69 ± 1.2 and 1584.89 ±0.8 while the IC50 of A549 and A549 - Sgol were 7943.3 ± 0.3 and 12589.3 ± 0.6. Conclusion： Sgol was highly expressed in A549/Taxotere, the docetaxel resistance may be reversed in NSCLC by decreasing the expression of Sgol.