目的:探讨经强力霉素（Dox）诱导后，丙氧鸟苷（GCV）对SCID小鼠乳腺癌的调控性治疗作用。方法: 重组逆转录病毒载体pRevTRE/HSVtk与pRevTet-On共转染乳腺癌细胞MCF-7，接种SCID小鼠成瘤后，腹腔内分别注射生理盐水（NS）、GCV及Dox+GCV治疗15 d。观测肿瘤体积和组织病理改变及用RT-PCR分析肿瘤组织有无HSVtk的表达。结果:乳腺癌SCID小鼠经Dox+GCV治疗15 d后，肿瘤体积明显减小，生长受抑，组间比较有显著性差异（P<0.05）;HE染色发现治疗组肿瘤有局部坏死，炎性细胞浸润。RT-PCR结果显示Dox诱导后肿瘤组织HSVtk表达较明显。结论: 在Dox的诱导作用下，GCV对可调控性自杀基因乳腺癌SCID小鼠有显著治疗作用。

Objective:To explore the ganciclovir（GCV） therapy on the severe combined immunodeficiency (SCID) breast cancer mice after HSVtk gene and Tet-On regulatory gene expression induced by doxycycline（Dox）. Methods:Co-transfections of pRevTRE/HSVtk and pRevTet-On were performed on MCF-7 cell line by using modified calcium phosphate precipitattion method respectively. After MCF/TRE/tk/Tet-On cell line was established，cells were inoculated into the SCID mice to form the human breast cancer in SCID mice. Regimen (GCV, GCV＋DOX, Normal Saline) was injected introperitoneally in SCID mice 15 days. The volume of tumor was measured and the tumor tissues were examined pathologically. HSVtk gene expression was analyzed by RT-PCR. Results:The human breast cancer in SCID mice was formed successfully by inoculated MCF/TRE/tk/Tet-On cells into the female SCID mice. In the GCV＋DOX-treated group, volume of tumors was shrank remarkably after 15 days' treatment and tumor growth were retarded compared with the control groups. There was significant difference between the GCV＋DOX-treated group and the control groups (P<0.05). Infiltrating cells were observed in tumors that injected with doxycycline followed by GCV treatment and cells were profoundly damaged stained with hematoxylin and eosin. The expression of tk gene in SCID mice tumors was also obeserved by RT-PCR analysis.Conclusions:The human breast cancer in SCID mice was formed successfully by implanted MCF/TRE/tk/Tet-On cells. The growth of tumor could be shrank remarkably with GCV treatment in our SCID mice under the doxycycline induction.

R730 Q782

CMB(美国中华医学会)基金(99-698)资助