Interleukin-17F suppresses hepatocarcinoma cell growth via inhibition of tumor angiogenesis.
Previous studies have shown that interleukin-17F (IL-17F) can markedly inhibit the angiogenesis of endothelial cells, implying that it may play a role in antiangiogenic therapy for tumors. To explore its effect on antiangiogenic therapy for hepatocellular carcinoma (HCC), we constructed a recombinant retrovirus vector RV-IL-17F expressing IL-17F, transfected SMMC-7721 human hepatocarcinoma cells with RV-IL-17F, and investigated the effect of transgene IL-17F expression on human hepatocarcinoma cells in vitro and in vivo in animal model. We demonstrated that IL-17F expression exerted no direct effect on in vitro proliferation and cell cycle of SMMC-7721 hepatocarcinoma cells, while it downregulated IL-6, IL-8, and VEGF expression in SMMC-7721 cells at both protein and mRNA levels and IL-17F-expressing supernatant from SMMC-7721/RV-IL-17F directly inhibited ECV304 vascular endothelial cell growth. Moreover, SMMC-7721/RV-IL-17F exhibited a significant decrease in tumor size and microvessel density as compared to the SMMC-7721/RV control when transplanted in nude mice. This retarded tumor growth in vivo elicited by IL-17F was associated with direct suppression of vascular endothelial cells and reduced expression of proangiogenic factors IL-6, IL-8, and VEGF leading to the inhibition of tumor angiogenesis. Thus, our results indicate that IL-17F, a novel antiangiogenic factor, may be useful in antiangiogenic therapy for HCC.
Xie
Yufeng
Y
Cell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, China.
Sheng
Weihua
W
Xiang
Jim
J
Ye
Zhenmin
Z
Yang
Jicheng
J
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008113:Liver Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C508606:CXCL8 protein, human; C440021:IL17F protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A