Reversing MultidrugResistant by RNA Interference

Authors: Long Sheng Maoming Xiong Cong Li Xiangling Meng

Publish Date: 2013/12/11

Volume: 20, Issue: 3, Pages: 541-548

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Abstract

Multidrug resistance MDR in hepatocellular carcinoma HC significantly impedes the effect of chemotherapy and is considered as a primary reason leading to its recurrences and metastasis The aim of present study was to explore new molecular targets for the reversal of MDR in HC by screening the adriamycin ADMinduced human MDRresistant HC cell subline Bel7402/ADM Small interfering RNAs siRNAs of four MDR1si326 MDR1si1513 MDR1si2631 and MDR1si3071 targeting MDR1 were designed and transfected into Bel7402/ADM cell strains The experiments involved the following mRNA expression of MDR1 gene by RTPCR Pglycoprotein Pgp expression by Western blot intracellular ADM accumulation flow cytometry and IC50 of ADM by a cytotoxic MTT assay Four siRNAs reversed MDR in HC mediated by MDR1 to varying degrees The expression level of MDR1 mRNA in cells of MDR1si326 or MDR1si2631 group 0190 ± 0038 or 0171 ± 0011 was more decreased The expression level of Pgp in cells of MDR1si326 group was the lowest The accumulation of ADM in cells of MDR1si326 or MDR1si2631 group 770 ± 35 or 754 ± 29 was more increased The IC50 of cells to ADM was lowest in MDR1si326 group 1132 ± 069 mg/L Compared with other three siRNAs MDR1si326 performed the optimal reversal effect of drug resistance in human HC Bel7402/ADMLS CL carried out the molecular genetic studies participated in the sequence alignment and drafted the manuscript XLM MMX conceived of the study and participated in its design and coordination and helped to draft the manuscript All authors read and approved the final manuscript MMX accepts full responsibility for the work and has accessed to the data and overseen the decision to publish

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