AIMS It has been demonstrated that reduced expression of alpha7 nicotinic acetylcholine receptor (α7nAChR) led to reduced chemotherapeutic drugs resistance in various cancer cells. However, whether small interfering RNA (siRNA) mediated knockdown of α7nAChR can reduce sorafenib (SOR) resistance in HCC cells remains to be determined. MATERIALS AND METHODS The effects of α7nAChR-siRNA in combination with SOR treatment was analyzed in human (HepG2) and mouse (Hepa 1-6) HCC cell lines. The MTT, DAPI staining and flow cytometry assays were applied to measure the cell viability, apoptosis and cell cycle progression of the cells. Also, the changes in the mRNA and protein levels of the α7nAChR were measured by quantitative real-time PCR and western blot analysis, respectively. KEY FINDINGS The results revealed that SOR increased both mRNA and protein levels of α7nAChR in HCC cells. Treatment with α7nAChR-siRNA abolished these effects. Also, SOR treatment in combination with α7nAChR-siRNA significantly sensitizes HCC cells to SOR cytotoxicity. This combination therapy significantly induced HCC cells apoptosis compared to SOR alone. SIGNIFICANCE These experimental results indicate that knockdown of α7nAChR by siRNA increased the SOR antitumor activity of HCC cells and suggests that this additive combination is a promising drug candidate for HCC therapy.

中文翻译：

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靶向α7烟碱乙酰胆碱受体的小分子干扰RNA使肝癌细胞对索拉非尼敏感。

目的已证明，α7烟碱乙酰胆碱受体（α7nAChR）的表达降低导致各种癌细胞对化疗药物的耐药性降低。然而，小干扰RNA（siRNA）介导的α7nAChR的敲低是否可以降低HCC细胞中索拉非尼（SOR）的耐药性尚待确定。材料和方法在人（HepG2）和小鼠（Hepa 1-6）HCC细胞系中分析了α7nAChR-siRNA联合SOR处理的作用。使用MTT，DAPI染色和流式细胞术测定来测量细胞的细胞活力，凋亡和细胞周期进程。另外，分别通过定量实时PCR和蛋白质印迹分析来测量α7nAChR的mRNA和蛋白质水平的变化。主要发现结果表明，SOR可提高HCC细胞中α7nAChR的mRNA和蛋白水平。用α7nAChR-siRNA处理消除了这些影响。同样，与S7ααnAChR-siRNA结合治疗显着使肝细胞癌对SOR细胞毒性敏感。与单独的SOR相比，这种联合疗法显着诱导了HCC细胞凋亡。意义这些实验结果表明，siRNA敲低α7nAChR可以增加HCC细胞的SOR抗肿瘤活性，并表明这种添加剂组合是用于HCC治疗的有希望的候选药物。与单独的SOR相比，这种联合疗法显着诱导了HCC细胞凋亡。意义这些实验结果表明，siRNA敲低α7nAChR可以增加HCC细胞的SOR抗肿瘤活性，并表明这种添加剂组合是用于HCC治疗的有希望的候选药物。与单独的SOR相比，这种联合疗法显着诱导了HCC细胞凋亡。意义这些实验结果表明，siRNA敲低α7nAChR可以增加HCC细胞的SOR抗肿瘤活性，并表明这种添加剂组合是用于HCC治疗的有希望的候选药物。