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 (ADM)-induced, human MDR-resistant HC cell subline Bel-7402/ADM. Small interfering RNAs (siRNAs) of four (MDR1si326, MDR1si1513, MDR1si2631 and MDR1si3071) targeting MDR1 were designed and transfected into Bel-7402/ADM cell strains. The experiments involved the following: mRNA expression of MDR1 gene by RT-PCR, P-glycoprotein (P-gp) 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 (0.190 ± 0.038 or 0.171 ± 0.011) was more decreased. The expression level of P-gp in cells of MDR1si326 group was the lowest. The accumulation of ADM in cells of MDR1si326 or MDR1si2631 group (77.0 ± 3.5 or 75.4 ± 2.9) was more increased. The IC50 of cells to ADM was lowest in MDR1si326 group (11.32 ± 0.69 mg/L). Compared with other three siRNAs, MDR1si326 performed the optimal reversal effect of drug resistance in human HC Bel-7402/ADM.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.