Abstract
Hypervascular hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated mortality. Angiogenesis is an important contributor to HCC progression and metastasis; therefore, inhibiting angiogenesis may be an effective method of treating HCC. Tumstatin is a novel type of efficient endogenous vascular endothelial cell growth inhibiting factor. The anti-angiogenic activity of tumstatin is localized to the 54-132 amino acid region (Tum-5). In a previous study performed by our group, the gene fragment encoding Tum-5 was cloned and inserted into a pLXSN retroviral vector. In the present study, the anti-angiogenic effects of Tum-5 and the antitumor effects exerted by the pLXSN-Tum-5 vector in vivo were investigated. The results demonstrated that pLXSN-Tum-5 significantly inhibited the growth of human umbilical vein endothelial cells compared with pLXSN, but had no obvious effect on HepG2 cell growth. Moreover, the antitumor and anti-angiogenic activity of Tum-5 was examined in vivo using a xenograft of H22 HCC cells. The results indicated that pLXSN-Tum-5 significantly inhibited tumor growth following 5 injections over 10 days. The size and weight of tumors in the pLXSN-Tum-5 group were lower than those in the saline and pLXSN groups. Furthermore, immunohistochemical analysis with CD31 antibodies indicated that the average microvessel density in the pLXSN-Tum-5 group were significantly lower than that in the saline and pLXSN groups. These results suggested that Tum-5 exerts its antitumor activity by suppressing vascular endothelial cells. The gene fragment of Tum-5 may be developed as an effective inhibitor of angiogenesis and used to treat patients with HCC.
Highlights
Hepatocellular carcinoma (HCC), one of the most common types of cancer in the world, is a hypervascular carcinoma
human umbilical vein endothelial cells (HUVECs) were transfected with pLXSN‐Tum‐5 or pLXSN virus at different
Tumor angiogenesis is a key process for the majority of solid tumors, since the growth and metastasis of malignant cells require the formation of new blood vessels [5,6,7,15,16]
Summary
Hepatocellular carcinoma (HCC), one of the most common types of cancer in the world, is a hypervascular carcinoma. Angiogenesis serves an important role in HCC progression, malignancy, metastasis and high rates of recurrence [1,2,3]. The development of genetic engineering technologies to target angiogenesis may be a novel and effective method of treating HCC. Angiogenesis enables tumor growth and metastasis to occur. It is the process by which tumor cells are provided with a supply of blood and nutrients [5,6,7]. Due to its extensive role in inducing cancer cell growth, tumor angiogenesis has become a novel and promising target for anticancer therapy. Inhibiting tumor angiogenesis may be an efficient way of preventing tumor occurrence and progression
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