RAD001 (everolimus) inhibits tumour growth in xenograft models of human hepatocellular carcinoma.
RAD001 (everolimus) inhibits tumour growth in xenograft models of human hepatocellular carcinoma.
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DOI：
10.1111/j.1582-4934.2008.00364.x
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发表时间：
2009-07
影响因子：
5.3
通讯作者：
Tran E
中科院分区：
文献类型：
--
作者：
Huynh H;Chow KH;Soo KC;Toh HC;Choo SP;Foo KF;Poon D;Ngo VC;Tran E
肝细胞癌（HCC）是世界上第五大最常见的恶性肿瘤，对现有的化疗具有高度耐药性。哺乳动物雷帕霉素靶蛋白（mTOR）在包括HCC在内的许多癌症中发挥调节蛋白质翻译、血管生成和细胞周期进展的作用。在本研究中，采用患者来源的肝癌皮下异种移植来研究mTOR抑制剂RAD001（依维莫司）对肿瘤生长、细胞凋亡和血管生成的影响。我们报道，口服RAD001对携带患者来源的肝癌异种移植物的小鼠产生剂量依赖性的肿瘤生长抑制。rad001诱导的生长抑制与mTOR下游靶点失活、VEGF表达和微血管密度降低、细胞增殖抑制、p27Kip1上调、p21Cip1/Waf1、Cdk-6、Cdk-2、Cdk-4、cdc-25C、cyclin B1和c-Myc下调有关。我们的数据表明，mTOR通路在肝癌细胞的血管生成、细胞周期进展和增殖中起着重要作用。我们的研究为mTOR抑制剂RAD001在HCC患者中的临床研究提供了强有力的依据。
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and highly resistant to available chemotherapies. Mammalian target of rapamycin (mTOR) functions to regulate protein translation, angiogenesis and cell cycle progression in many cancers including HCC. In the present study, subcutaneous patient-derived HCC xenografts were used to study the effects of an mTOR inhibitor, RAD001 (everolimus), on tumour growth, apoptosis and angiogenesis. We report that oral administration of RAD001 to mice bearing patient-derived HCC xenografts resulted in a dose-dependent inhibition of tumour growth. RAD001-induced growth suppression was associated with inactivation of downstream targets of mTOR, reduction in VEGF expression and microvessel density, inhibition of cell proliferation, up-regulation of p27Kip1 and down-regulation of p21Cip1/Waf1, Cdk-6, Cdk-2, Cdk-4, cdc-25C, cyclin B1 and c-Myc. Our data indicate that the mTOR pathway plays an important role in angiogenesis, cell cycle progression and proliferation of liver cancer cells. Our study provides a strong rationale for clinical investigation of mTOR inhibitor RAD001 in patients with HCC.
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影响因子：
2.4
作者：
Huynh H;Nguyen TT;Chow KH;Tan PH;Soo KC;Tran E
通讯作者：
Tran E
影响因子：
4
作者：
Huang, S;Houghton, PJ
通讯作者：
Houghton, PJ
影响因子：
11.2
作者：
Liu, Li;Cao, Yichen;Carter, Christopher
通讯作者：
Carter, Christopher
影响因子：
45.3
作者：
Abou-Alfa, Ghassan K.;Schwartz, Lawrence;Saltz, Leonard B.
通讯作者：
Saltz, Leonard B.
影响因子：
8
作者：
Lee, JW;Soung, YH;Lee, SH
通讯作者：
Lee, SH