| Co-Investigator(Kenkyū-buntansha) |
MABUCHI Hideaki Osaka Medical College, Faculty of medicine, Research Associate, 医学部, 助手 (80340545)
NOMURA Eiji Osaka Medical College, Faculty of medicine, Assistant Professor, 医学部, 講師 (30288732)
YAMAMOTO Tetsuhisa Osaka Medical College, Faculty of medicine, Research Associate, 医学部, 助手 (50330072)
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| Research Abstract |
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
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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
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