Cell-killing effects of adenovirus-mediated transfer of CD :: UPP gene directed by mdr1 promoter on Taxol-resistant ovarian cancer cells / 肿瘤

ABSTRACT

Objective: To evaluate the specific killing effects of the adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene (CDUPP) directed by the mdrl promoter combined with 5-fluorocytosine (5-FC) on Taxol-resistant ovarian cancer cells in vitro and in vivo. Methods: The adenovirus vector carrying the mdrl-CD UPP gene was amplified, purified, and transferred into Taxol-resistant A2780/Taxol ovarian cancer cells and A2780 cells. The expression of mdrl and CD UPP was detected by RT-PCR. After addition of 5-FC, the cell proliferation was assessed by MTT assay. The female BALB/c nude mice bearing tumor xenografts were injected adenovirus vector containing mdrl-CD UPP gene and then administered 5-FC. The growth of transplanted tumors was observed. Results: Mdrl and CD UPP gene were stably expressed in A2780/Taxol cells. The growth speed of A2780/Taxol cells was significantly slower than A2780 cells after transfection. Transfection of CD UPP gene combined with administration of 5-FC induced bystander effect of A2780/ Taxol cells on neighbor cells. The tumor growth in test group was significantly inhibited compared with control group (569.10 ± 187.93) mm3 vs (2 111.98 ± 230.82) mm3, P < 0.01. Conclusion: The mdrl promoter in an adenovirus vector regulates the specific expression of CD UPP in A2780/Taxol cells. This system specifically kills Taxol-resistant ovarian cancer cells.