Vector-mediated Tum-5 expression in neovascular endothelial cells for treating hepatocellular carcinoma
Vector-mediated Tum-5 expression in neovascular endothelial cells for treating hepatocellular carcinoma
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DOI：
10.3892/etm.2017.4127
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发表时间：
2017-04-01
影响因子：
2.7
通讯作者：
Gai, Xiaodong
中科院分区：
文献类型：
--
作者：
Li, Chun;Guan, Xingang;Gai, Xiaodong
富血管性肝细胞癌（HCC）是癌症相关死亡的主要原因之一。血管生成是 HCC 进展和转移的重要贡献者；因此，抑制血管生成可能是治疗HCC的有效方法。 Tumstatin是一种新型高效内源性血管内皮细胞生长抑制因子。 tumstatin 的抗血管生成活性位于 54-132 个氨基酸区域 (Tum-5)。在我们小组之前进行的一项研究中，编码Tum-5的基因片段被克隆并插入到pLXSN逆转录病毒载体中。在本研究中，研究了 Tum-5 的抗血管生成作用和 pLXSN-Tum-5 载体在体内发挥的抗肿瘤作用。结果表明，与pLXSN相比，pLXSN-Tum-5显着抑制人脐静脉内皮细胞的生长，但对HepG2细胞的生长无明显影响。此外，使用 H22 HCC 细胞的异种移植物在体内检查了 Tum-5 的抗肿瘤和抗血管生成活性。结果表明，10 天内注射 5 次后，pLXSN-Tum-5 显着抑制肿瘤生长。 pLXSN-Tum-5组的肿瘤大小和重量低于盐水组和pLXSN组。此外，CD31抗体的免疫组织化学分析表明，pLXSN-Tum-5组的平均微血管密度显着低于盐水组和pLXSN组。这些结果表明Tum-5通过抑制血管内皮细胞发挥其抗肿瘤活性。 Tum-5的基因片段可能被开发为有效的血管生成抑制剂并用于治疗HCC患者。
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.