Study on the Relationship Between XIAP Gene and Resistance of Taxol in Ovarian Cancer

YUE Chi, LI Ran-hong, CHEN Chen. et al

Abstract

To research the expression of X-linked inhibitor of apoptosis protein gene (XIAP) on paclitaxel resistance in ovarian cancer. Methods A2780 and A2780/T cells were treated with paclitaxel respectively at the concentrations of 5 ng/mL, 10 ng/mL, 20 ng/mL ,40 ng/mL, 80 ng/mL, 160 ng/mL, 320 ng/mL, then the inhibition rate of cells were detected by MTT assay. The expression of XIAP mRNA and protein among the A2780 and A2780/T cells treated respectively with paclitaxel at the concentration of 100 ng/mL was detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. The A2780/T cells were divided into blank group, empty group, small interfering RNA (siRNA) XIAP group and siRNA-non-specific group. The expression of XIAP mRNA and protein of four groups were detected by RT-qPCR and Western blot. Apoptotic rate of these groups with addition of paclitaxel at the concentrations of 0 ng/mL, 1 000 ng/mL, 1 500 ng/mL, 2 000 ng/mL and 2 500 ng/mL were detected by flow cytometry. Results After the treatments on A2780 and A2780/T cells with the different concentrations of paclitaxel, the inhibition rate of A2780 cells were gradually increased with the increased paclitaxel concentrations (P<0.05), while there were no obvious differences in A2780/T cells (P>0.05). After the treatment on these cells with paclitaxel at the concentration of 100 ng/mL, the expression of XIAP mRNA was lower than that non-treatment with paclitaxelin A2780 cells (P<0.05), and the expression of XIAP mRNA in the A2780/T cells were no statistical significance between the treatment group and non-treatment group with paclitaxel (P>0.05). However, the expression of A2780/T cells’XIAP mRNA and protein treated with paclitaxel were higher than A2780 cells’ (P<0.05). The expression of XIAP mRNA and protein in siRNA-XIAP group was lower than those of other groups (P<0.05). The apoptotic rateof siRNA-XIAP group was higher than those of other groups treated with the paclitaxel at concentrations of 2 000 ng/mL and 2 500 ng/mL (P<0.05). Conclusion XIAP’s high expression on mRNA and protein was correlated with ovarian cancer paclitaxel-resistance, specific siRNA can promote cell apoptosis by reducing the expression of XIAP, and increase the sensitivity of drug-resistant cancer cells to paclitaxel.

 

Keywords: XIAP, Ovarian cancer, Paclitaxel, Chemoresistance siRNA 


Full Text:

PDF


References


CLARKE-PEARSON DL. Screening for ovarian cancer. N Engl J Med,2009,361(2): 170-177.

CHIENJR, ALETTI G, BELL DA, et al. Molecular pathogenesis and therapeutic targets in epithelial ovarian cancer. J Cell Biochem,2007,102(5): 1117-1129.

CHAUDHARY AK, YADAV N, BHAT ТА, et al. A potential role of X-linked inhibitor of apoptosis protein in mitochondrial membrane permeabilization and its implication in cancer therapy. Drug Discov Today,2016,21 (1);38-47.

SCHIMMER AD. DA LI LI S, BATEY RA, et al. Targeting XIAP for the treatment of malignancy. Cell Death Differ, 2006,13(2):179-188.

CHEN W, ZENG WS, LI X, et al. MicroRNA-509-Зр increases the sensitivity of epithelial ovarian cancer cells to cisplatin-induced apoptosis. Pharmacogenomics, 2016, 17 ( 3): 187-197.

GE GQ, ZHANG W, NIU LG .et al. miR-215 functions as a tumor suppressor inepithelial ovarian cancer through regulation of the X-chromosome-linked inhibitor of apoptosis. Oncol Reports,2016,35(3); 1816-1822.

MA JJ, CHEN BL, XIN XY. XIAP gene downregulation by small interfering RNA inhibits proliferation, induces apoptosis, and reverses the cisplatin resistance of ovarian carcinoma. Eur J Obstet Gynecol Reprod Biol,2009, 146(2) ; 222-226.


Refbacks

  • There are currently no refbacks.