ABSTRACT
Ovarian cancer is among the most prevalent gynecological malignancies around the globe. Nonetheless, chemoresistance continues to be one of the greatest obstacles in the treatment of ovarian cancer. Therefore, understanding the mechanisms of chemoresistance and identifying new treatment options for ovarian cancer patients is urgently required. In this study, we found that the mRNA and protein expression levels of PRDX1 were significantly increased in cisplatin resistant A2780/CDDP cells. Cell survival assays revealed that PRDX1 depletion substantially increased ovarian cancer cell sensitivity to cisplatin, docetaxel, and doxorubicin. Additionally, PRDX1 significantly increased GSTP1 activity, resulting in multidrug resistance. Biochemical experiments showed that PRDX1 interacted with GSTP1 through Cysteine 83, which regulated GSTP1 activity as well as chemotherapy resistance in ovarian cancer cells. Our findings indicate that the molecular chaperone activity of PRDX1 is a promising new therapeutic target for ovarian cancer.
ABSTRACT
Mutidrug resistance (MDR) severely blocks the successful management of breast cancer. Overexpression of MDR1/p-gp accounts for the major factor in the development of MDR. ß-arrestin 2 has been reported to widely involve in multiple aspects of tumor development. In order to verify whether ß-arrestin 2 regulates mutidrug resistance in breast cancer, we analyzed the protein expression levels of ß-arrestin 2 and MDR1/p-gp by immunohistochemistry in 106 paraffin-embedded human breast tissue samples. There was a positive correlation between ß-arrestin 2 and MDR1/p-gp protein expression (P = 0.016). Changes in MDR1/p-gp mRNA and protein levels were examined by quantitative real-time reverse polymerase chain reaction (qRT-PCR) and western blotting. Silencing of ß-arrestin 2 evidently down-regulated the expression of MDR1/p-gp in transfected ADM cells. In contrast, overexpression of ß-arrestin 2 had the opposite changes in MDA-MB-231 and MCF-7 cells. MTS assay revealed that silencing of ß-arrestin 2 increased the sensitivity to anti-cancer drugs to some extent. On the other hand, overexpression of ß-arrestin 2 had the opposite effects. Our above data demonstrate that ß-arrestin 2 plays a vital role in the regulation of MDR1/p-gp expression in Breast cancer.
Subject(s)
Antineoplastic Agents/therapeutic use , Arrestins/metabolism , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Drug Resistance, Multiple/genetics , Drug Resistance, Neoplasm/genetics , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Antineoplastic Agents/pharmacology , Arrestins/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/pathology , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , beta-Arrestin 2 , beta-ArrestinsABSTRACT
Aim To determine whether membrane cytokeratin 8(CK8 )and BCRP expression cooperatively contributed to multidrug resistance(MDR)in MCF-7/MX cells.Methods MCF-7/MX cells were transfected with specific anti CK8-siRNAs and anti BCRP-siRNAs via LipofectAMINE2000.The expression of CK8 and BCRP was determined using Western blot,and membrane staining was observed by laser confocal microscopy.Sensitivity to chemical drugs was examined by Sulforhodamine B method.Results The expression levels of cell surface CK8 and BCRP were obviously reduced by siRNAs,and inhibition of CK8 and BCRP expression could effectively restore the sensitivity to drugs and reverse MDR phenotype of MCF-7/MX cells.Conclusions CK8 together with BCRP may play significant roles in conferring the multifactorial MDR phenotype of MCF-7/MX cells,but may act independently via potentially different mechanisms.Combinational approaches that target multiple drug-resistance-related molecules/pathways in cancer cells may represent more efficacious strategies to overcome MDR.
ABSTRACT
Purpose:To detect the action of arsenic trioxide(As 2O 3) on the expression of tumor drug-resistant protein. Methods:APL cell line MR 2 resistant to all-trans retinoic acid(ATRA) was used for in vitro studies. APL cell line NB 4 was used for control. The expressions of P-glycoprotein(Pgp), multidrug resistance protein(MRP)were determined by immunocytochemical assays. Results:The expression of Pgp was significantly higher in MR 2 cell line(30%-40%) than in NB 4 cell line(10%-20%)(P
ABSTRACT
Objective To explore the mechanism of reversal of mutidrug resistance of GBC-SD cell lines by grape seed polyphenols(GSP).Methods GBC-SD cell lines were used to determine the effect of GSP.MTT assay was adopted to evaluate the cytotoxity(IC_(50)),RT-PCR were used to determine MDR1mRNA,(P-gp),bcl-2 and cellular adriamycin was measured by flow cytometry.Results In non-toxic(3?g/mL) and low toxic(6?g/mL) comcentration of GSP treated group(P
