Retrovirus-mediated tk gene therapy of implanted human breast cancer in nude mice under the regulation of Tet-On

Abstract

Tight regulation of the therapeutic gene expression is critical in gene therapy. In this report, a doxycycline (Dox)-regulated retrovirus-mediated gene expression system was used to study the effects of suicide gene therapy on human breast cancer cell line MCF-7 and the nude mice model of implanted human breast cancer. To render the expression of suicide gene under control, we used two pseudoviruses simultaneously, RevTRE/HSVtk and RevTet-On, to infect MCF-7 cells or xenografts of nude mice. When infected by the pseudoviruses and followed by Dox and Ganciclovir (GCV) treatment, MCF-7 cells were arrested at S phase and the growth was suppressed. We then evaluated the antitumor efficiency of this system in vivo through studying the mice bearing human breast cancer xenografts. Compared with control groups, the HSVtk mRNA level increased significantly in tumor tissues, mass of the tumors shrank remarkably, and tumor necrosis features occurred after treatment with Dox and GCV. These data suggest that suicide gene therapy using the Dox-induced Tet-On-controlled HSVtk gene expression system is a feasible method to treat human breast cancer.

STGC3 inhibits xenograft tumor growth of nasopharyngeal carcinoma cells by altering the expression of proteins associated with apoptosis

“…The cells were trypsinized, suspended in phosphate-buffered saline (PBS) and 0.2 mL containing 2×10 6 cells was inoculated under the right armpit of each mouse. The mice were also injected intraperitoneally with either doxycycline (Dox, 20 mg/kg; Roche, Switzerland) or an equal volume of PBS every day for 28 days (Zeng et al , 2006b). Tumor growth was monitored by measuring two perpendicular diameters with vernier calipers every three days, and tumor volume was calculated using the formula W 2 xLx0.52, where L is the length and W is the width of the tumor.…”

The cell death and DNA damages caused by the Tet-On regulating HSV-tk/GCV suicide gene system in MCF-7 cells

“…In our previous study, we focused on the significant anti-tumor effects of HSV-tk/GCV/Tet-On. We found that this regulation system has a better therapeutic achievement by adjusting the dosage of GCV, or inducing the adjustment of gene expression level in suicide gene therapy system in our continuous exploration [4]. However, the anti-tumor effect of the regulation system remains unknown.…”

Genetically engineered suicide gene in mesenchymal stem cells using a Tet-On system for anaplastic thyroid cancer

“…Antitumor drugs are able to kill some types of cancer cells; however, antitumor drugs generally produce significant toxicity in normal organs, generate host morbidity, and induce treatment related mortality [36–38]. Suicide gene therapy also generates systemic toxicity and byproducts.…”