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人端粒酶逆转录酶启动子控制和单纯疱疹病毒胸苷激酶武装的腺病毒治疗肾细胞癌。

Human telomerase reverse-transcriptase promoter-controlled and herpes simplex virus thymidine kinase-armed adenoviruses for renal cell carcinoma treatment.

机构信息

Tianjin Medical University, Tianjin, People's Republic of China ; Tianjin Medical University, Tianjin, People's Republic of China ; Tianjin Medical University, Tianjin, People's Republic of China ; Tianjin Medical University, Tianjin, People's Republic of China.

出版信息

Onco Targets Ther. 2013 Apr 18;6:419-26. doi: 10.2147/OTT.S41978. Print 2013.

DOI:10.2147/OTT.S41978
PMID:23723709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3665657/
Abstract

New treatment strategies are required for renal cell carcinoma (RCC) due to its relative insensitivity to conventional radio- and chemotherapies. The promising strategy of tumor inhibition using human telomerase reverse transcriptase (hTERT)-controlled herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) in the hTERT promoter-driven HSV-TK/GCV suicide gene system was investigated. Tumor volume, weight, relative proliferation rate, and cell-apoptosis levels were examined in mice injected with adenovirus (Ad)-hTERT-HSV-TK and GCV. Increased cell death occurred following treatment with Ads carrying hTERT-HSV-TK/GCV or cytomegalovirus promoter-controlled (CMV)-HSV-TK/GCV for human RCC 786-0 and fibroblast MRC-5 cells. In mice, Ad-hTERT-HSV-TK/GCV more specifically inhibited tumor and RCC xenograft growth than Ad-CMV-HSV-TK/GCV (P < 0.05). Furthermore, Ad-hTERT-HSV-TK/GCV did not significantly damage normal fibroblasts or organ systems (heart, lung, liver, brain, kidney, and spleen). Thus, Ad-hTERT-HSV-TK/GCV is an effective RCC inhibitor in human cells in vitro and in vivo mouse models, indicating potential usefulness in RCC-targeted gene therapy.

摘要

由于肾细胞癌 (RCC) 对常规放化疗相对不敏感，因此需要新的治疗策略。本研究采用人端粒酶逆转录酶 (hTERT) 启动子控制的单纯疱疹病毒胸苷激酶/更昔洛韦 (HSV-TK/GCV)自杀基因系统，研究了使用 hTERT 控制的单纯疱疹病毒胸苷激酶/更昔洛韦 (HSV-TK/GCV) 抑制肿瘤的有前途的策略。在注射腺病毒 (Ad)-hTERT-HSV-TK 和 GCV 的小鼠中，检查了肿瘤体积、重量、相对增殖率和细胞凋亡水平。携带 hTERT-HSV-TK/GCV 或巨细胞病毒启动子控制 (CMV)-HSV-TK/GCV 的 Ads 处理后，人 RCC 786-0 和成纤维细胞 MRC-5 细胞的细胞死亡增加。在小鼠中，Ad-hTERT-HSV-TK/GCV 比 Ad-CMV-HSV-TK/GCV 更特异性地抑制肿瘤和 RCC 异种移植物生长 (P < 0.05)。此外，Ad-hTERT-HSV-TK/GCV 对正常成纤维细胞或器官系统（心脏、肺、肝、脑、肾和脾）没有明显损伤。因此，Ad-hTERT-HSV-TK/GCV 是体外人细胞和体内小鼠模型中有效的 RCC 抑制剂，表明在 RCC 靶向基因治疗中具有潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/2196d0c1fece/ott-6-419Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/f34443fd03f6/ott-6-419Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/a06abf9a98a7/ott-6-419Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/dcc04c790b6e/ott-6-419Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/ae1eb7f071d2/ott-6-419Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/61f9e2702f0c/ott-6-419Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/2196d0c1fece/ott-6-419Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/f34443fd03f6/ott-6-419Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/a06abf9a98a7/ott-6-419Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/dcc04c790b6e/ott-6-419Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/ae1eb7f071d2/ott-6-419Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/61f9e2702f0c/ott-6-419Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/3665657/2196d0c1fece/ott-6-419Fig6.jpg

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