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MicroRNA-155在肝细胞癌对索拉非尼抗药中的作用研究 被引量:3

Effect of microRNA-155 on sorafenib resistance in hepatocellular carcinoma
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摘要 目的探讨微小RNA155(microRNA-155,miR-155)在肝细胞癌(hepatocellular carcinoma,HCC)对索拉非尼(sorafenib)抗药中的作用。方法将miR-155抑制慢病毒(miR-155 inhibitor)转染miR-155表达相对较高的SMMC-7721细胞,而miR-155过表达慢病毒(miR-155)转染miR-155表达相对较低的Hep G2细胞;用荧光定量PCR(qPCR)检测经慢病毒转染的SMMC-7721细胞及HepG2细胞miR-155表达量,以验证慢病毒转染效果;通过CCK-8法及流式细胞术检测各组细胞经索拉非尼作用后的存活率及凋亡情况;用Western blot检测凋亡相关蛋白活性caspase-3表达量,从而进一步探究各组细胞凋亡情况。结果与对照组相比,转染miR-155抑制慢病毒的SMMC-7721细胞表达miR-155明显下调(P<0.01),经索拉非尼处理后其存活率明显降低(P<0.05),而索拉非尼诱导其凋亡明显增加(P<0.01),其活性caspase-3表达量明显上调(P<0.01);miR-155过表达慢病毒转染HepG2细胞后,则相反。结论 miR-155参与肝细胞癌对索拉非尼的抗药,有希望成为一个肝癌治疗的新靶标。 Aim To investigate the effect of microRNA-155(miR-155)on sorafenib resistance in hepatocellular carcinoma(HCC).Methods Lentivirus mediated miR-155 inhibition was transfected into SMMC-7721 cells, while lentivirus mediated miR-155 overexpression was transfected into HepG2 cells.The level of miR-155 was evaluated by qPCR.Cell viability and apoptosis were analyzed by cell counting kit-8(CCK-8)assay and flow cytometry, respectively.The protein expression of activated caspase-3 was measured by Western blot.Results Compared to control group, the expression of miR-155 was significantly downregulated in miR-155 inhibition lentivirus infected SMMC-7721 cells(P〈0.01), sorafenib treatment markedly suppressed cell viability(P〈0.05)and increased cell apoptosis(P〈0.01), as well as enhanced the expression of activated caspase-3(P〈0.01).However, HepG2 cells were infected by miR-155 overexpression lentivirus which deserved completely opposite results.Conclusion miR-155 may participate in sorafenib resistance in HCC and provide a promising molecular target for the treatment of HCC.
作者 吕峰 王伟 艾麦提.牙森 金鑫 李德卫 LYU Feng WANG Wei AI Mai Ti·Ya Sen JIN Xin LI De-wei(Dept of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China)
出处 《中国药理学通报》 CAS CSCD 北大核心 2017年第5期657-662,共6页 Chinese Pharmacological Bulletin
基金 国家自然科学基金资助项目(No 81470898)
关键词 微小RNA155 肝细胞癌 索拉非尼 抗药 慢病毒 活性caspase-3 mircoRNA-155 hepatocellular carcinoma sorafenib drug resistance lentivirus activated caspase-3
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  • 1Wilhelm S M,Carter C,Tang L,et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis[ J]. Cancer Res,2004,64(19) :7099 - 109.
  • 2Strumberg D, Clark J W, Schwartz B, et al. Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib : a review of four phase I trial in patients with advanced refractory solid tumors[J]. Oncologist,2007,12 (4) :426 - 37.
  • 3Richly H,Henning B F,Strumberg D,et al. Results of a Phase 1 trial of sorafenib ( BAY 43-9006) in combination with doxorubicin in patients with refractory solid tumors [ J ]. Ann Oncol, 2006,17 (5) :866 -73.
  • 4Strumberg D, Richly H, Hilger R A, et al. Phase I clinical and pharmacokinetic study of the novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY43-9006 in patients with advanced refractory solid tumors [ J ]. J Clin Oncol, 2005,23 (5) :965 -72.
  • 5Moore M,Hirte H W,Siu L,et al. Phase I study to determine the safety and pharma-cokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006 ,administered for 28 days on/7 days off in patients with advanced, refractory solid tumors [J]. Ann Oncol, 2005,16(10) : 1688 -94.
  • 6Ratain M J, Eisen T, Stadler W M, et al. Phase lI placebo-controlled randomized discontinuatoin trial of Sorafenib in patients with advanced renal cell carcinoma[J]. J Clin Oncol,2006,24(16) :2505 -12.
  • 7Escudier B,Eisen T,Bukowski R M,et al. Sorafenib in advanced clear-cell carcinoma[J]. N Engl J Med,2007 ,356( 2 ) :125 -34.
  • 8Ryan C W, Goldman B H, Crawford E D, et al. Sorafenib with interferon alfa-2b as first-line treatment of advanced renal carcinoma: a phase Ⅱ study of the Southwest Ontology Group[ J ]. J Clin Oncol,2007,25(22) :3296 - 301.
  • 9Gollob J A,Rathmell W K,Wright J J,et al. Phase Ⅱ trial of sorafenib plus interferon-2b (IFN-2b) as first-or second-line therapy in patients with metastatic renal cell cancer [ J ]. J Clin Oncol, 2007,25(22) :3288 -95.
  • 10Ranze O, Hofmann E, Hoeffkes H G, et al. Renal cell cancer presented with leptomeningeal carcinomatosis effectively treated with sorafenib [ J ], Onkologie,2007,30 ( 8-9 ) :450 - 1.

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