Downregulation of gene MDR1 by shRNA to reverse multidrug-resistance of ovarian cancer A2780 cells

• Published in: Journal of cancer research and therapeutics 2012-04, Vol.8 (2), p.226-231
• Main Authors: Zhang, Hongyi, Wang, Jing, Cai, Kai, Jiang, Longwei, Zhou, Dandan, Yang, Cuiping, Chen, Junsong, Chen, Dengyu, Dou, Jun
• Format: Article
• Language: English
• Subjects: Animal experimentation; Animals; Antineoplastic Agents - pharmacology; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Cancer; Care and treatment; Cell Line, Tumor; Cell Survival - drug effects; Chemotherapy; Cisplatin - pharmacology; Down-Regulation; Drug resistance; Drug Resistance, Multiple - genetics; Drug Resistance, Neoplasm - genetics; Female; Gene expression; Gene Knockdown Techniques; Genetic aspects; Humans; Medical research; Mice; Mice, Inbred BALB C; Mice, Nude; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Paclitaxel - pharmacology; Paclitaxel - therapeutic use; Physiological aspects; Proteins; RNA Interference; RNA, Small Interfering - genetics; Taxoids - pharmacology; Tumor Burden; Vincristine - pharmacology; Xenograft Model Antitumor Assays
• ISSN: 0973-1482; 1998-4138
• DOI: 10.4103/0973-1482.98975

To explore the effects of downregulated multidrug-resistance P-glycoprotein (MDR1/ABCB1) and reversed multidrug-resistance in human A2780 ovarian cancer cells. Three shRNAs targeting the MDR1 gene were synthesized, and cloned into plasmid pSUPER-enhanced green fluorescent protein 1 (EGFP1). The formed pSUPER-EGFP1-MDR1-shRNAs were transfected into the A2780 cells, respectively, and the quantitative reverse transcription polymerase chain reaction and western blot were used respectively to determine the MDR1 expression. The multidrug-resistance (MDR) of the MDR1-shRNAs transfected A2780 cells to chemotherapy drugs in vitro and in tumor-bearing nude mice were respectively evaluated. The MDR1 shRNA expression resulted in decreased P-glycoprotein expression in the transfected A2780 cells. The MDR1-shRNA2 transfected cells showed that the sensitivities to chemotherapy drugs were higher than other shRNAs transfected A2780 cells, and that the formed tumor in mice grew slower than those of other mice after paclitaxel was injected into tumor-bearing nude mice. Our data demonstrates that the RNA interference could knock down gene MDR1 and reduce the P-glycoprotein expression, and partly reverse the MDR of A2780 cells in vitro and in vivo. These results suggest that MDR-1 is an effective therapeutic target for human ovarian caner treatment.