Preliminary Study On The Effect Of MAP3K3 Mediated NF-?B Signaling Pathway In Chemotherapy Resistance Of Ovarian Carcinoma

Objective: Interfering MAP3K3 expression and / or blocking NF-?B signal pathway,to detect MAP3K3 expression in ovarian carcinoma cells,combined with NF-?B signal pathway-related factors and apoptosis-related protein expression changes and analysis the role of MAP3K3 mediated NF-?B signal pathway in chemotherapy resistance of ovarian carcinoma.Methods: MAP3K3 specific interference expression plasmid and MAP3K3 eukaryotic expression plasmid were transfected into SKOV3 and OV2008 cells respectively.The transfection efficiency of MAP3K3 was detected by Western Blot and q RT-PCR.MTT assay was used to detect the sensitivity of cells to cisplatin,paclitaxel and TNF-?.TUNEL was used to detect cell apoptosis.The expression of NF-?B signaling pathway-related factors and the apoptosis-related factors were observed before and after treatment with NF-?B signal-specific blocker QNZ.Results:(1)MAP3K3 protein and m RNA were highly expressed in SKOV3 cells and were lower in OV2008 cells.The sensitivity of OV2008 cells to cisplatin was significantly higher than SKOV3 cells.(2)After knockdown of MAP3K3 in SKOV3,the expression of p-P65,p-I?B? and anti-apoptotic protein Bcl-2 were down-regulated,and the expression of pro-apoptotic protein cleaved-caspase3 and BAX were up-regulated.(3)After overexpression of MAP3K3 in OV2008,the number of cisplatin-induced apoptosis was significantly decreased,the sensitivity of cisplatin to cells was weakened and the growth of cells was accelerated,with the expression of cleaved-caspase3 and BAX were down-regulated,the expression of p-P65,p-I?B? and anti-apoptotic protein Bcl-2 were up-regulated.(4)The sensitivity of cells to paclitaxel and TNF-? was increased in SKOV3 cells after knockdown of MAP3K3.The sensitivity of cells to paclitaxel and TNF-? was decreased after overexpression of MAP3K3 in OV2008.The sensitivity of both cells to paclitaxel and TNF-? was enhanced after blocking NF-?B signaling pathway.Conclusion: Differential expression level of MAP3K3 in ovarian carcinoma cell lines may be related to the cell chemotherapy resistance.The high expression of MAP3K3 promotes the activation of NF-?B signaling pathway and the expression of downstream antiapoptotic protein,inhibits the expression of pro-apoptotic protein and reduces the ability of chemotherapeutic drugs induced apoptosis,suggesting that MAP3K3 may promotes chemotherapy resistance in ovarian carcinoma cells by mediating NF-?B signaling pathway.