Myeloid differentiation factor 88 promotes cisplatin chemoresistance in ovarian cancer.

Abstract

To investigate regulatory effects and associated mechanisms of myeloid differentiation factor 88 (MyD88) on cisplatin chemoresistance in human ovarian cancer (OC) cells. The expression of MyD88 in SKOV3/DDP cells was restrained by short interfering RNA (siRNA) of MyD88. Cell viability and proliferation in the presence or absence of cisplatin were detected by Cell Counting Kit-8 (CCK-8). The expression of p-Akt protein, X-linked inhibitor of apoptosis protein (XIAP), and multidrug resistance protein 1 (MRP1) was detected by Western blot analysis. After Protein Kinase B (PKB/Akt) signal pathway was inhibited by the p-Akt inhibitor (LY294002) and the expression of MRP1 was restrained by siRNA of MRP1, CCK-8 was used to examine the cell proliferation after treatment with cisplatin. After the expression of MyD88 in SKOV3/DDP cells was restrained, the cell proliferation was inhibited, the cisplatin resistance decreased and the half maximal inhibitory concentration (IC50) reduced to 38 % of the control group (P < 0.01). The increased expression of p-Akt, XIAP, and MRP1 in SKOV3/DDP cells after cisplatin treatment was also repressed by the downregulation of MyD88. Furthermore, the inhibition of PKB/Akt signal pathway or expression of MRP1 both could decrease the cisplatin resistance of SKOV3/DDP cells and the IC50 decreased to 75 and 53 % of the control group (P < 0.01, P < 0.05), respectively. MyD88 promoted cisplatin chemoresistance in human OC cells through activating PKB/Akt signal pathway, and enhancing the expression of XIAP and MRP1. MyD88 might be a new target of the novel pharmacological treatments for cisplatin-resistant OC.