The effect of vitamin D3 and ketoconazole combination on VDR-mediated P-gp expression and function in human colon adenocarcinoma cells: implications in drug disposition and resistance.
作者： Bhavani P. Kota , John D. Allen , Basil D. Roufogalis
DOI: 10.1111/J.1742-7843.2011.00693.X
关键词:
摘要: Abstract: The vitamin D3 metabolite 1,25-dihydroxycholecalciferol (DHC) and analogues derived from it are being investigated as potential agents for the treatment of cancer. Combining ketoconazole (KTZ) with DHC has been recommended to enhance anticancer activity DHC. exerts its biological activities through D receptor (VDR). VDR is recognized be a regulator P-glycoprotein (P-gp), member ABC transporter family well known role in multidrug resistance cancer chemotherapy. We have effect adding KTZ together on P-gp expression functional consequences induction intestinal human colonic adenocarcinoma cells LS174T cells. increased by two times, addition further four times. combination DHC + KTZ also significantly expression, consistent enhanced increase this combination. was accompanied function, measured decreased Rh123 accumulation In addition, colchicine cytotoxicity dose-sensitive manner, cytotoxicity, indicating chemo-protective KTZ, P-gp. results study raise possibility that may decrease effectiveness chemotherapy promoting P-gp-mediated drug resistance.
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