人乳腺癌裸鼠移植瘤的体外抗生素诱导基因治疗

目的探讨Tet调控下体外抗生素诱导基因治疗人乳腺癌裸鼠移植瘤的可行性。方法构建人乳腺癌BALB/C裸鼠移植瘤模型,制备有感染活性的重组逆转录病毒RevTRE/HSVtk与RevTet-On。观察体外强力霉素(Dox)诱导,丙氧鸟苷(GCV)和逆转录病毒作用后移植瘤生长的变化及组织病理改变,分析其对乳腺癌裸鼠移植瘤的调控性治疗作用。结果乳腺癌裸鼠治疗后,肿瘤体积明显减小,生长受抑,生存周期延长,组间比较有显著性差异(P<0.05)。瘤体HE染色显示治疗组肿瘤局部有炎性细胞浸润和强嗜酸性细胞。RT-PCR结果显示Dox诱导后瘤体组织HSVtk表达较明显。结论通过逆转录病毒介导Tet调控,可以在体外抗生素Dox诱导下对人乳腺癌裸鼠移植瘤模型进行基因治疗,杀伤肿瘤细胞。

Gene Therapy for Human Breast Carcinoma Xenografts in Nude Mice Induced by Antibiotics in Vivo

Objective Using Tet regulation system,the feasibility of gene therapy for human breast carcinoma xenografts in nude mice induced by antibiotics in vivo were investigated in this study.Methods Mouse breast cancer model was established by transferring human breast cancer cells subcutaneously into the BALB/C nude mice to make xenografts.Recombinant retroviruses containing HSVtk and Tet-On gene were constructed respectively for treatment.The growth of tumor was tested and pathological analysis was performed after ganciclovir(GCV) and retroviruses treatment induced by doxycycline(Dox).The antitumor effect was observed to evaluate the regulatory therapy in breast cancer model of nude mice.Results After GCV and retroviruses treatment,under induction of Dox,volume of tumors of nude mice model was decreased remarkably,tumor growth was retarded and survival period was prolonged compared with the control groups(P<(0.05)).Some of infiltrating inflammatory cells and strong eosinophil cells could be observed in the tumor mass stained with hematoxylin and eosin.Conclusion Recombinant retroviruses containing Tet regulation system and suicide gene can successfully used in cancer gene therapy and killed tumor cells in breast cancer model of nude mice after GCV treatment induced by antibiotics(Dox) in vivo.