文献类型：会议论文

英文题名：Overcoming multidrug resistance in human carcinoma cells by an antisense oligodeoxynucleotide-doxorubicin conjugate in vitro and in vivo

作者：Ren, Yuhong[1];Wang, Yong[1];Zhang, Yufei[1];Wei, Dongzhi[1]

机构：[1]E China Univ Sci & Technol, Inst Biochem, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

会议论文集：7th International Symposium on Polymer Therapeutics

会议日期：MAY 26-28, 2007

会议地点：Ctr Invest Principe Felipe, Valencia, SPAIN

主办单位：Ctr Invest Principe Felipe

语种：英文

外文关键词：multidrug resistance; antisense oligodeoxynucleotide-doxorubicin conjugate; P-glycoprotein; KB-A-1 cells

摘要：Multidrug resistance (MDR), a major obstacle to successful cancer chemotherapy, may be induced by amplification of the MDR1 gene and overexpression of the P-glycoprotein (P-gp), which acts as drug efflux pump decreasing intracellular drug accumulation. In this study, an antisense oligodeoxynucleotide--doxorubicin conjugate was used to overcome MDR in a human carcinoma-resistant cell line, both in vitro and in vivo, through downregulation of P-gp expression and mRNA levels. Compared with the unmodified antisense-oligodeoxynucleotide (AS-ODN), the conjugate markedly inhibited P-gp expression and mRNA levels. With in vitro treatment with the conjugate, the intracellular accumulation of doxorubicin (DOX) was increased 4.4-fold compared to treatment with DOX alone; by contrast, a 2.2-fold increase was observed when treated with AS-ODN alone. In the in vivo studies, it was approximately 3.5-fold higher compared to the control group treatment with DOX alone and 2.1-fold higher than found with AS-ODN. The weight of tumors formed was markedly decreased after conjugate treatment as compared to either treatments with AS-ODN or DOX alone. Furthermore, treatment with combinations of the agents appeared to be well tolerated. These results suggest that a strategy using the conjugate in combination with antitumor drugs may comprise a powerful treatment for MDR.