EphA1 receptor silencing by small interfering RNA has antiangiogenic and antitumor efficacy in hepatocellular carcinoma.

Abstract

The Eph family of receptor tyrosine kinases has emerged as one of the pivotal regulators of tumor angiogenesis. EphA1, the first identified member of the Eph receptor family, has been found to be overexpressed in several types of human tumors. A recent report indicated that EphA1 was overexpressed in hepatocellular carcinoma (HCC) and that elevated expression of EphA1 can promote proliferation of HCC cells through stimulation by exogenous Ephrin-A1. To investigate the role of EphA1 in angiogenesis and progression of HCC, we down-regulated EphA1 by RNA interference (RNAi) technology, in an HCC-derived cell line with a high level of EphA1 expression. We established a stable knockdown clone named SiEphA1/Huh-7. The knockdown resulted in decreased proliferation of Huh-7 cells, as well as decreased motility and invasion capability in vitro. siRNA-based EphA1 knockdown also down-regulated the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2 and -9. Interestingly, the suppression of EphA1 expression in Huh-7 cells reduced their outgrowth when inoculated in the subcutaneous space in the flank of nude mice, presumably through angiogenesis inhibition since microvessel density was found to be inhibited.

• Authors: Gang Chen, Yi Wang, Mengtao Zhou, Hongqi Shi, Zhengping Yu, Yefan Zhu, Fuxiang Yu
• Journal: Oncology reports (Oncol Rep) Vol. 23 Issue 2 Pg. 563-70 (Feb 2010) ISSN: 1791-2431 [Electronic] Greece
• PMID: 20043122 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• RNA, Small Interfering
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Receptor, EphA1

Topics

• Angiogenesis Inhibitors (pharmacology, therapeutic use)
• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Carcinoma, Hepatocellular (blood supply, drug therapy, genetics, pathology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Liver Neoplasms (blood supply, drug therapy, genetics, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• NIH 3T3 Cells
• RNA, Small Interfering (pharmacology, therapeutic use)
• Receptor, EphA1 (antagonists & inhibitors, genetics)
• Treatment Outcome
• Tumor Cells, Cultured
• Vascular Endothelial Growth Factor A (genetics)
• Xenograft Model Antitumor Assays