Bax-induced apoptosis as a novel gene therapy approach for carcinoma of the cervix

Gynecologic Oncology
W K HuhD T Curiel

Abstract

The transfer of tumor suppressor genes has been shown to revert the malignant phenotype. In this regard, bax is a pro-apoptotic molecule that also functions as a tumor suppressor. The purpose of this study was to evaluate bax as a gene therapeutic in the context of cervical cancer. Efficiency of viral transduction in cervical cancer cell lines and primary cervical cancer cells was evaluated with an adenoviral vector encoding green fluorescent protein and luciferase, respectively. We generated a recombinant adenoviral vector that encodes the bax gene under inducible conditions. To this end, expression of this pro-apoptotic gene was controlled by a Cre-LoxP system. Following infection with the recombinant bax adenovirus, the viability of cervical cancer cell lines and primary cervical cancer cells was evaluated using crystal violet staining and FACS analysis. Apoptotic cell death was monitored using annexin V staining. High levels of viral infection were observed in all cervical cancer cell lines (>85%) and primary cervical cancer cells. Significant cytotoxicity was seen in all cervical cancer cells lines and, more importantly, patient-derived primary cervical cancer cells. Moreover, bax-mediated cell death occurred via an apopto...Continue Reading

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Citations

Jun 25, 2002·Expert Opinion on Biological Therapy·Lloyd D Graham
Jun 20, 2008·The Journal of Gene Medicine·Kenya OkumuraToshiro Tagawa
Oct 18, 2005·Gynecologic Oncology·Parameshwar J MahasreshtiDavid T Curiel
Mar 6, 2004·Cancer Gene Therapy·Tsuyoshi HondaTimothy J McDonnell

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