He Lei, Gong Han-Xian, Li Xiang-Pen, Wang Yi-Dong, Li Yi, Huang Jun-Jian, Xie Dan, Kung Hsiang-Fu, Peng Ying
Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, P.R. China.
Oncol Lett. 2013 Sep;6(3):748-752. doi: 10.3892/ol.2013.1470. Epub 2013 Jul 16.
A 27-kDa C-terminal fragment of human telomerase reverse transcriptase, hTERTC27, has previously been reported to inhibit the growth and tumorigenicity of HeLa human cervical cancer cells and U87-MG human glioblastoma multiforme cells. However, the antitumor effects of hTERTC27 in hepatoma and its underlying mechanisms are unclear. In the current study, the therapeutic effect of hTERTC27, mediated by recombinant adenovirus, in hepatocellular carcinoma (HCC) was explored and to investigate the possible mechanisms. The results indicated that recombinant adenovirus carrying hTERTC27 (rAdv-hTERTC27) effectively inhibited the growth and induced apoptosis of the Hepa 1-6 HCC cells. Dendritic cells transduced with rAdv-hTERTC27 were highly effective at inducing antigen-specific T cell proliferation and increasing the activated cytotoxicity of T cells against Hepa 1-6 cells. HCC was inhibited significantly when a single dose of 5×10 pfu rAdv-hTERTC27 was administered intravenously. In summary, the results of this study demonstrated that rAdv-hTERTC27 may serve as a reagent for intravenous administration when combined with telomerase-based gene therapy and immunotherapy for cancer.
据此前报道，人端粒酶逆转录酶的一个27 kDa C端片段hTERTC27可抑制人宫颈癌HeLa细胞和多形性胶质母细胞瘤U87-MG细胞的生长及致瘤性。然而，hTERTC27在肝癌中的抗肿瘤作用及其潜在机制尚不清楚。在本研究中，探讨了重组腺病毒介导的hTERTC27对肝细胞癌（HCC）的治疗效果，并研究其可能的机制。结果表明，携带hTERTC27的重组腺病毒（rAdv-hTERTC27）有效抑制了Hepa 1-6肝癌细胞的生长并诱导其凋亡。用rAdv-hTERTC27转导的树突状细胞在诱导抗原特异性T细胞增殖以及增强T细胞对Hepa 1-6细胞的活化细胞毒性方面非常有效。静脉注射单剂量5×10 pfu rAdv-hTERTC27时，肝癌得到显著抑制。总之，本研究结果表明，rAdv-hTERTC27在与基于端粒酶的癌症基因治疗和免疫治疗联合使用时，可作为一种静脉给药试剂。
