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首页> 外文期刊>World Journal of Gastroenterology >Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma.
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Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma.

机译：hTERT启动子调节的肿瘤选择性溶瘤腺病毒在人肝细胞癌中的抗肿瘤活性。

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AIM: To construct a tumor-selective replication-competent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice. RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cellsand resulted in apoptosis and necrosis of cancer cells. CONCLUSION: hTERT promoter-regulated replicative adenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.
机译：目的：使用人端粒酶逆转录酶（hTERT）的修饰启动子构建具有肿瘤选择性复制能力的腺病毒（RCAd）SG300。方法：体外和体内评估SG300在肝细胞癌中的抗肿瘤作用。通过MTT测定的体外细胞生存力用于评估SG300的肿瘤选择性溶瘤和安全性特征，并且在已建立的裸鼠肝细胞癌模型中评估SG300的体内抗肿瘤活性。结果：SG300可以以低感染复数（MOI）裂解肝癌细胞，但即使在高MOI下也不会影响正常细胞的生长。在肝细胞癌的Hep3B和SMMC-7721异种移植模型中，SG300均具有明显的抗肿瘤作用，导致肿瘤体积减小。它对肿瘤细胞的选择性溶瘤和对正常细胞的安全性也优于ONYX-015。肿瘤标本的病理检查表明，SG300在癌细胞中选择性复制，并导致癌细胞凋亡和坏死。结论：hTERT启动子调控的复制型腺病毒SG300具有较好的癌选择性复制能力，可以特异性杀伤多种具有端粒酶活性的癌细胞，因此具有靶向肝细胞癌的潜力。

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