Abstract:

Background and purpose: Multi-drug resistance is a major reason for the chemotherapy failure of human ovarian cancer. Sorcin was found overexpression in drug resistance tumors and it may be the target of multidrug resistance reversal. The present article was aimed to study the effect and mechanism of Sorcin silencing on drug resistance of human ovarian cancer SKOV3/CDDP cell lines. Methods: The stable Sorcin silencing SKOV3/CDDP cell lines were established. MTS assay, flow cytometry was used to analyze the intra-cellular Rh-123 content, cells apoptosis and cycle. Real-time, Western blot and report gene assay were used to analyze the expression changes of genes,including MDR1, MPR1, Survivin, Bcl-2, p-Akt and NF-κB. Results: Sorcin inhibition enhanced the drug sensitivity of SKOV3/CDDP cells, increased the intra-cellular Rh-123 content and cell apoptosis, and arrested cell cycle in G2/M.The protein levels of MDR1, MPR1, Survivin, Bcl-2, p-Akt were down-regulated, the mRNA levels of MDR1 of Sh-Sorcin-1 and Sh-Corcin-2 group were decreased to 42.3% and 26.5% of untransfected control, MRP1 were decreased to 33.2% and 18.9% of untransfected control, Survivin were decreased to 36.2% and 29.6% of untransfected control, Bcl-2 were decreased to 54.6% and 46.7% of untransfected control, transcriptional activity of NF-κB were decreased to 56.3% and 38.4% of untransfected control respectively inSKOV3/CDDP cell lines after Sorcin silence. Conclusion: Sorcin silencing could reverse SKOV3/CDDP drug resistance and enhance drug sensitivity, which involves the decreased phosphorylation level of Akt and transcriptional activity of NF-κB.

Key words: Ovarian Cancer, Sorcin, Drug resistance