Gene Therapy for Ovarian Cancer Using Adenovirus-Mediated Transfer of Cytosine Deaminase Gene and Uracil Phosphoribosyltransferase Gene Directed by MDR1 Promoter

Shi Lu, Xiaoyi Wang, Lan Xiao, Liqiong Cai, Yuan Zhang, Hongbo Wang and Zehua Wang

volume 6 | issue 3

March 2007
Pages: 397 - 404

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Objective: To evaluate the specific killing effects of the adenoviral vector in which the CD∷UPP genes were directed by the MDR1 promoter on Taxol-resistance ovarian cancer cells in vitro and in vivo. Methods: Taxol-resistance (A2780/Taxol, SKOV3/Taxol) ovarian cancer cells and Taxol- sensitive (A2780, SKOV3) ovarian cancer cells were infected with adenovirus vector carrying the CD∷UPP gene driven by the MDR1 promoter, followed with 5-fluorocytosine administration. Sensitivity to 5-fluorocytosine (5-FC) was analyzed. The AdMDR1-CD∷UPP was subcutaneously injected into the xenografts of the nude mice and 5-FC intraperitoneally. The overall survival and anti-tumor effects were observed. Results: In vitro, AdMDR1-CD∷UPP showed a stronger cytotoxicity in A2780/Taxol cells and SKOV3/Taxol cells than that in A2780 cells and SKOV3 cells. Subcutaneous injection of AdMDR1-CD∷UPP into the xenografts of mice bearing tumors of A2780/Taxol cells could significantly suppress the tumor growth and prolong survival as compared with the group of A2780 cells. Conclusion: AdMDR1-CD∷UPP in combination with 5-FC is an effective approach to suppress the growth of Taxol-resistant ovarian cancer.