| 摘要: |
| ［摘要］ 目的 观察辛伐他汀对非小细胞肺癌（NSCLC）细胞增殖和免疫逃逸的影响，并探讨其机制。方法 用改进MTT法检测不同浓度辛伐他汀、RhoA siRNA处理后A549细胞的增殖情况；用Real-time RT-PCR检测抗免疫逃逸相关因子即主要组织相容性复合体Ⅰ类(MHCⅠ,又称HLA-A)和肽转运蛋白（TAP1）的基因表达；用RhoA活性测定法观察RhoA活性变化；用Lipofectamine 2000转染siRNA。结果 辛伐他汀能浓度依赖性（10～30 μmol/L）地抑制A549细胞增殖，增强HLA-A和TAP1基因表达，抑制RhoA活性(P<0.05或<0.01)。用0.1 μmol/L RhoA siRNA抑制RhoA活性后，也能显著抑制A549细胞增殖，增加HLA-A和TAP1基因表达（P<0.01）。但RhoA siRNA联合应用辛伐他汀不能产生协同效应，而与单用RhoA siRNA的作用相似（P>0.05）。结论 辛伐他汀主要依赖于抑制A549细胞的RhoA活性，从而增加HLA-A和TAP1表达，减少免疫逃逸和细胞增殖。 |
| 关键词: 辛伐他汀 非小细胞肺癌 细胞增殖 免疫逃逸 RhoA |
| DOI：10.3969/j.issn.1674-3806.2013.08.01 |
| 分类号:R 96 |
| 基金项目:国家自然科学基金青年科学基金资助项目（编号：81201622）；国家自然科学基金地区资助项目（编号：81260324） |
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| Effects of simvastatin on cell proliferation and immune escape of non-small cell lung cancer |
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LIU Bing，YANG Jie
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Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
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| Abstract: |
| ［Abstract］ Objective To evaluate the effects of simvastatin on cell proliferation and immune escape of human non-small cell lung cancer(NSCLC) as well as the underlying mechanisms.Methods Cell proliferation was determined using a modified MTT assay after the treatment with different concentrations of simvastatin, or RhoA siRNA in A549 cells. The gene expression of anti-immune escape factor, major histocompatibility complex class Ⅰ(MHCⅠ, also known as HLA-A) and peptide transporter protein(TAP1) were detected by real-time RT-PCR. The change of RhoA activity was measured by a microplate reader in A549 cells treated with simvastatin, or RhoA siRNA. SiRNA transfection was done using lipofectamine 2000.Results Simvastatin(10～30 μmol/L) significantly reduced the proliferation, enhanced gene expression of HLA-A and TAP1 and inhibited RhoA activity of A549 cells in concentration-dependent manner(P<0.05 or P<0.01). Moreover, inhibition of RhoA activity with 0.1 μmol/L RhoA siRNA also resulted in a substantial inhibition of proliferation and increased gene expression of HLA-A and TAP1 of 549 cells(P<0.01). However, combination treatment of RhoA siRNA and simvastatin exerted no synergistic effects in 549 cells compared with the specific siRNA treatment alone(P>0.05).Conclusion Simvastatin can suppress A549 cells proliferation and immune escape primarily through inhibition of RhoA activity and thereby increasing the gene expression of HLA-A and TAP1. |
| Key words: Simvastatin Non-small cell lung cancer（NSCLC） Cell proliferation Immune escape RhoA |
