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用于治疗人类乳腺癌的溶瘤单纯疱疹病毒载体

Oncolytic herpes simplex virus vectors for the treatment of human breast cancer.

作者信息

Liu Ren-bin, Rabkin Samuel D

机构信息

Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.

出版信息

Chin Med J (Engl). 2005 Feb 20;118(4):307-12.

Abstract

BACKGROUND

Oncolytic herpes simplex virus (HSV) vectors can be used for cancer therapy as direct cytotoxic agents, inducers of anti-tumor immune responses, and as expressers of anti-cancer genes. In this study, the efficacy of HSV vectors, G47Delta and NV1023 were examined for the treatment of the human breast cancer.

METHODS

Human breast cancer MDA-MB-435 cells were cultured or implanted subcutaneously in BALB/c nude mice. The cells or tumors were inoculated with G47Delta or NV1023, and cell killing or inhibition of tumor growth determined. Both viruses contained the LacZ gene and expression in infected cells was detected with X-gal histochemistry.

RESULTS

G47Delta and NV1023 were highly cytotoxic to MDA-MB-435 cells in vitro at very low multiplicities of infection. X-gal staining of infected tumor cells in vitro and in vivo illustrated the replication and spread of both viruses. G47Delta and NV1023 inoculation inhibited tumor growth and prolonged mouse survival. Both vectors behaved similarly.

CONCLUSIONS

Oncolytic HSV vectors, G47Delta and NV1023, were extremely effective at killing human breast cancer cells in vitro and in tumor xenografts in vivo. This novel form of cancer therapy warrants further investigation and consideration of clinical application.

摘要

背景

溶瘤单纯疱疹病毒(HSV)载体可作为直接细胞毒性剂、抗肿瘤免疫反应诱导剂以及抗癌基因表达载体用于癌症治疗。在本研究中,检测了HSV载体G47Delta和NV1023治疗人类乳腺癌的疗效。

方法

将人乳腺癌MDA-MB-435细胞培养或皮下植入BALB/c裸鼠体内。用G47Delta或NV1023接种细胞或肿瘤,测定细胞杀伤或肿瘤生长抑制情况。两种病毒均含有LacZ基因,通过X-gal组织化学检测感染细胞中的表达。

结果

在非常低的感染复数下,G47Delta和NV1023在体外对MDA-MB-435细胞具有高度细胞毒性。体外和体内感染肿瘤细胞的X-gal染色显示了两种病毒的复制和传播。接种G47Delta和NV1023可抑制肿瘤生长并延长小鼠生存期。两种载体表现相似。

结论

溶瘤HSV载体G47Delta和NV1023在体外和体内肿瘤异种移植中对人乳腺癌细胞具有极强的杀伤作用。这种新型癌症治疗方法值得进一步研究和考虑临床应用。

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