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超声靶向破坏微泡介导单纯疱疹病毒胸苷激酶基因治疗小鼠肝癌。

Ultrasound-targeted microbubble destruction mediated herpes simplex virus-thymidine kinase gene treats hepatoma in mice.

机构信息

Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, PR China.

出版信息

J Exp Clin Cancer Res. 2010 Dec 23;29(1):170. doi: 10.1186/1756-9966-29-170.

Abstract

OBJECTIVE

The purpose of the study was to explore the anti-tumor effect of ultrasound -targeted microbubble destruction mediated herpes simplex virus thymidine kinase (HSV-TK) suicide gene system on mice hepatoma.

METHODS

Forty mice were randomly divided into four groups after the models of subcutaneous transplantation tumors were established: (1) PBS; (2) HSV-TK (3) HSV-TK+ ultrasound (HSV-TK+US); (4) HSV-TK+ultrasound+microbubbles (HSV-TK+US+MB). The TK protein expression in liver cancer was detected by western-blot. Applying TUNEL staining detected tumor cell apoptosis. At last, the inhibition rates and survival time of the animals were compared among all groups.

RESULTS

The TK protein expression of HSV-TK+MB+US group in tumor-bearing mice tissues were significantly higher than those in other groups. The tumor inhibitory effect of ultrasound-targeted microbubble destruction mediated HSV-TK on mice transplantable tumor was significantly higher than those in other groups (p < 0.05), and can significantly improve the survival time of tumor-bearing mice.

CONCLUSION

Ultrasound-targeted microbubble destruction can effectively transfect HSV-TK gene into target tissues and play a significant inhibition effect on tumors, which provides a new strategy for gene therapy in liver cancer.

摘要

目的

本研究旨在探讨超声靶向破坏微泡介导单纯疱疹病毒胸苷激酶(HSV-TK)自杀基因系统对小鼠肝癌的抗肿瘤作用。

方法

建立皮下移植瘤模型后,将 40 只小鼠随机分为四组:(1)PBS;(2)HSV-TK;(3)HSV-TK+超声(HSV-TK+US);(4)HSV-TK+超声+微泡(HSV-TK+US+MB)。采用 Western blot 检测肝癌组织中 TK 蛋白的表达。应用 TUNEL 染色检测肿瘤细胞凋亡。最后,比较各组动物的抑制率和生存时间。

结果

荷瘤鼠组织中 HSV-TK+MB+US 组的 TK 蛋白表达明显高于其他各组。超声靶向微泡破坏介导 HSV-TK 对小鼠移植瘤的抑瘤作用明显高于其他各组(p<0.05),并能明显提高荷瘤鼠的生存时间。

结论

超声靶向微泡破坏能有效将 HSV-TK 基因转染至靶组织,对肿瘤发挥显著抑制作用,为肝癌的基因治疗提供了新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b8f/3022677/e4fc2554f81b/1756-9966-29-170-1.jpg

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