Medical treatment research by the gene cluster (EPR-1, dCK, and TP) which guides antineoplastic drug susceptibility reinforcement

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EPR-1 cDNA, a potential survivin antisense, was ligated into a plasmid vector (pMTN2) with metallothionein promoter. Then HT29 human colon adenocarcinoma cells (with positive survivin expression) were transfected with the pMTN2-EPR-1 plasmid vector. Apoptosis was induced in HT29-AS33 and HT29-AS49 subolones with high EPR-1 expression in the presence of Zinc and furthermore sensitivity to Cis-DDP and 5-FU in vitro was increased. Then, on the basis of future clinical development, EPR-1 expressing adenovirus vector (ad.CMV-EPR-1) was made and the in vivo antitumor treatment was assessed on nude mouse HT29 xenografts. When the xenografts were 8mm or more, Ad.CMV-EPR1 and Ad.CMV-LacZ were injected to the tumor bearing mice once. In former group tumor formation was reduced to 1/4 comparing to the controls. This, suggested that the effect was due to HT29 cell line apoptosis induction. In addition, efficacy of CDDP or 5-FU combination with Ad.CMV-EPR-1 was enhanced, with reduction in tumor vol … More ume of 25% and 16% respectively (Eur J Cancer, in Press). Moreover, we have previously shown that transfected cells with plasmid vector expressing dThdPase(TP) cDNA were more sensitive to 5'-DFUR and 5-FU(Br J Cancer 75,1997). Therefore, at the time of this study, TPcDNA (1.5 kb) was transferred to EcoRI site of a retroviral vector, -pNV7 and transfected murine adenocarcinoma cell lines of MC38-TP and MC38-Neo were obtained. In Western blot and ELISA analysis the expression of TP was detected in MC38-TP, but not in the controls and the growth rate of both subclones was identical. As increased sensitivity to 5-FU,5'-DFUR and Capecitabine was significantly observed in vitro for the former group, in vivo experiment was also studied using subcutaneously inoculated MC38-TP mouse models which confirmed the enhancement of 5'-DFUR and Capecitabine chemotherapeutic effect in MC38-TP (data in submission). Such chemosensitivity related gene studies may be useful to provide effective improvement in current cancer chemotherapy. Less