title: 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.
authors.affiliation: Gynaecology and Obstetrics Department, Zhengzhou People's Hospital, 33 Huanghe Road, Zhengzhou, 450000, China, drliuguanghong@163.com.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Liu
authors.forename: Peijie
authors.initials: P
authors.lastname: Du
authors.forename: Zhanxin
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D002945:Cisplatin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D053594:Myeloid Differentiation Factor 88; D051057:Proto-Oncogene Proteins c-akt; D051636:X-Linked Inhibitor of Apoptosis Protein; C507779:MYD88 protein, human; C496866:XIAP protein, human; C421109:multidrug resistance-associated protein 1