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Rho激酶抑制剂法舒地尔作用BTBD7-ROCK2信号通路抑制肝细胞癌侵袭运动 被引量:2

Suppression of hepatocellular carcinoma invasion and metastasis by Rho-kinase inhibitor Fasudil through inhibition of BTBD7-ROCK2 signaling pathway
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摘要 目的:观察Rho激酶抑制剂法舒地尔(Fasudil)对人高侵袭潜能HCC细胞株3(human high metastatic liver cancer cells 3,HCCLM3)侵袭转移的影响,并且探讨其作用的机制。方法:应用100 mol/L Fasudil作用于HCCLM3细胞,采用肌动蛋白微丝荧光染色和侵袭小室实验观察HCCLM3细胞的运动侵袭能力。HCCLM3细胞经过处理后分为阴性对照组、Fasudil作用组、BTBD7干扰组,通过Western印迹检测BTB/POZ结构域蛋白7(BR-C,ttk and bab/pox virus domain containing 7,BTBD7)、Ras同系物家族成员C(ras homolog family member C,Rho C)、Rho关联卷曲螺旋蛋白激酶2(Rhoassociated,coiled-coil containing protein kinase 2,ROCK2)、MMP2和MMP9蛋白表达水平,酶谱分析法检测MMP2和MMP9活性水平。BTBD7干扰组作为阳性对照。结果:Fasudil处理后HCCLM3侵袭运动能力下降,BTBD7,Rho C,ROCK2蛋白表达下调,MMP2和MMP9活性降低,与阴性对照组比较差异有统计学意义(均P<0.01)。结论:Fasudil具有干预BTBD7-ROCK2信号通路、抑制HCC侵袭转移的重要作用。 Objective: To explore the eff ect of Fasudil on the invasion and metastatic abilities of human high metastatic liver cancer cells (HCCLM3) and the underlying mechanisms. Methods: HCCLM3 cells were incubated with 100 μmol/L Fasudil. Fluorescence staining forF-actin and Transwell assay were performed to observe the invasion ability of HCCLM3 cells. HCCLM3 cells were divided into 3 groups: a negative control group, a Fasudil group and a BTB/POZ domain containing 7 (BTBD7)-siRNA group. Western blot assay was performed to detect the expression levels of BTBD7, ras homolog family member C (RhoC) and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2), matrix metalloproteinases 2 (MMP2) and MMP9. Zymogram analysis method was performed to detect the expression activities of MMP2 and MMP9. hTe BTBD7-siRNA group was served as a positive control. Results: In HCCLM3 cells treated with Fasudil, the invasion ability was significant decreased compared with the control group, concomitant with the down-regulated expression levels of BTBD7, RhoC and ROCK2 protein as well as the decreased activities of MMP2 and MMP9. Conclusion: Fasudil plays an important role in interfering BTBD7-ROCK2 signaling pathway and suppressing the invasion and metastasis of hepatocellular carcinoma.
出处 《中南大学学报(医学版)》 CAS CSCD 北大核心 2014年第12期1221-1227,共7页 Journal of Central South University :Medical Science
基金 国家自然科学基金(81372630 81372631)~~
关键词 肝细胞癌 BTB/POZ结构域蛋白7 Rho关联卷曲螺旋蛋白激酶2 法舒地尔 侵袭转移 hepatocellular carcinoma BTB/POZ domain containing 7 Rho-associated,coiled-coil containing protein kinase 2 Fasudil invasion and metastasis
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参考文献1

  • 1Yuko Takeba,Naoki Matsumoto,Minoru Watanabe,Sachiko Takenoshita-Nakaya,Yuki Ohta,Toshio Kumai,Masayuki Takagi,Satoshi Koizumi,Takeshi Asakura,Takehito Otsubo.The Rho kinase inhibitor fasudil is involved in p53-mediated apoptosis in human hepatocellular carcinoma cells[J].Cancer Chemotherapy and Pharmacology.2012(6) 被引量:1

同被引文献29

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