The effect and mechanism of Sorcin silencing on drug resistance of human ovarian cancer SKOV3/CDDP cell lines / 中国癌症杂志

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 multi-drug 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.