期刊
JOURNAL OF MOLECULAR MEDICINE-JMM
卷 88, 期 8, 页码 817-827出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00109-010-0623-4
关键词
Hypoxia; HIF-1 alpha; HCC; Chemotherapy
资金
- Deutsche Forschungsgemeinschaft [Cr 133/2-1, Cr 133/2-2, Cr 133/2-3, Graduiertenkolleg 276/4]
- Berliner Krebsgesellschaft [CRFF200804]
Hepatocellular carcinoma (HCC) is a hypervascularized tumor entity with association of arterial vessel density with poor prognosis. The hypoxia-inducible transcription factor HIF-1 alpha represents a pivotal regulator of angiogenesis and is thought to determine the angiogenic nature of HCC. However, the precise role of HIF-1 alpha during the pathogenesis of HCC remains elusive. We established a functional inactivation of HIF-1 alpha in vitro and in vivo via RNAi and Cre/loxP-mediated recombination, respectively, to determine HIF-1 alpha's role for tumor growth and chemosensitivity in transgenic and orthotopic murine HCC models. HIF-1 alpha-deficient HCC cells displayed significantly reduced anchorage-independent growth and enhanced sensitivity toward etoposide, while basic cellular proliferation was unaffected. Analysis of gross tumor growth failed to detect reduced growth of HIF-1 alpha-deficient tumors in the orthotopic and the transgenic HCC model, respectively. In line with the in vitro data, treatment of HIF-1 alpha-deficient tumors with etoposide resulted in greater antiproliferative efficacy when compared to wild-type mice. Taken together, our study does not support a pivotal role of HIF-1 alpha for tumor growth and angiogenesis in two murine HCC models. However, our data point toward a significant function of HIF-1 alpha in determining chemosensitivity of HCC and therefore warrant validation of HIF-1 alpha-inhibitors as adjuvant therapeutic agents in clinical studies of human HCC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据