Zhang Youlei, Li Li, Wang Yi, Zhang Jun, Wei Gongtian, Sun Yanfu, Shen Feng
Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200433, China.
Biochem Biophys Res Commun. 2007 Jun 22;358(1):124-9. doi: 10.1016/j.bbrc.2007.04.068. Epub 2007 Apr 19.
Invasion and metastasis are key features of human hepatocellular carcinoma (HCC). Heparanase is an endoglycosidase that can degrade extracellular matrix by cleaving heparan sulfate chains of heparan sulfate proteoglycan, thus playing important roles in the invasion and metastasis of human cancers. Heparanase has been detected in various human cancers and regarded as a prospective target in human cancer treatments. However, the effects of inhibiting the expression of heparanase on human HCC have not been fully evaluated. In this article we show that downregulating the expression of heparanase either by antisense oligodeoxynucleotide or by RNA interferencing can significantly reduce the expression of heparanase in SMMC7721 human HCC cells, leading to inhibition of the invasiveness, metastasis, and angiogenesis of HCC cells both in vitro and in vivo. Our results suggest that genetic downregulation of the expression of heparanase may serve as an efficient cancer therapeutic for human HCC.
侵袭和转移是人类肝细胞癌（HCC）的关键特征。乙酰肝素酶是一种内切糖苷酶，可通过切割硫酸乙酰肝素蛋白聚糖的硫酸乙酰肝素链来降解细胞外基质，从而在人类癌症的侵袭和转移中发挥重要作用。乙酰肝素酶已在多种人类癌症中被检测到，并被视为人类癌症治疗中的一个潜在靶点。然而，抑制乙酰肝素酶表达对人类肝癌的影响尚未得到充分评估。在本文中，我们表明，通过反义寡脱氧核苷酸或RNA干扰下调乙酰肝素酶的表达，可显著降低SMMC7721人肝癌细胞中乙酰肝素酶的表达，从而在体外和体内抑制肝癌细胞的侵袭、转移和血管生成。我们的结果表明，基因下调乙酰肝素酶的表达可能是一种有效的人类肝癌治疗方法。
