Experimental Study Of Drug-resistant Cancer Gene Therapy

Objective To explore the effect on biological behavior of chemotherapy-resistant tumor cells by human wild-type p53. GM-CSF and B7-1 genes mediated via recombinant adenovirus. Methods p53-abnormal KB-v200 (VCR resistant) and KB-s (VCR sensitive) cell lines were used as model tumor cells, which are resistant and sensitive to chemotherapeutic drugs, respectively After infected with recombinant adenovirus carning human wild-type p53, GM-CSF and B7-1 genes, changes in biological behavior (including drug sensitivity) of these two kinds of gene-transduced cancer cells were observed . Results both of the cell lines were susceptible to adenovirus, all of three exogenous genes (p53. GM-CSF and B7-1) could be effectively expressed in these cell lines, and their growth was inhibited, apoptosis was induced. The drug-pumping-out function of Pgp glycoprotein on the cytomembrane of drug-resistant KB-v200 cells was markedly affected 48h after transfection of the recombinant adenovirus. revealed by increase of the amount of rhodamine 123 accumulated in the cells. The MTT assay also indicated the reversal of their sensitivity to VCR drugs. However, the results of RT-PCR detection showed the transcription levels of mdr-1 gene and mrp gene were all raised. In vivo experiment in nude mice demonstrated reduction of tumorigemcity of the KB-v200 cells or KB-s cells infected with the recombinant adenovirus, and increase of their sensitivity to VCR. Conclusion The clinical application of this recombinant adenovirus carrying multiple gene in combination with chemotherapeutic agents might be more effective in treatment of tumors with MDR.