Effect Of Atractylenolide I On The Expression Of PD-L1、PD-1 And TDOmRNA In Human Ovarian Cancer SKOV-3 And A2780 Cells

Background and objectives:Epithelial ovarian cancer(EOC)is a complex and challenging malignancy tumor.Five year survival is typically 46%,Advances in therapies have improved survival,but overall burden of mortality remains high,accounting for 4.2% of deaths worldwide.Immunologic escaping is one of the main factors leading to the poor prognosis of EOC patients.EOC is regarded as immunogenic and immune responses may play an important role in prognosis.In recent years,research datas show that Atractylenolide I(AO-1)is a naturally occurring sesquiterpene lactone,which modulates ovarian cancer cell-mediated immunosuppression by blocking MD-2/TLR4complex-mediated My D88/NF-κB signaling in vitro.The programmed death receptor(PD-1)and its ligand 1(PD-L1)are considered to be the key regulatory factors of tumor-induced immunosuppression,and they play an important role in tumor immune escape as a control point of immune sentinel.Indoleamine 2,3 dioxygenase(IDO)and tryptophan 2,3-dioxygenase(TDO)is a heme rate-limiting enzyme in the catabolism of Trp along the kynurenine pathway,which can mediate antimicrobialand immunomodulation.Studies have shown that The expression of PD-L1 and TDO was found in ovarian cancer.inhibiting the expression and activity of PD-L1/TDO can improve immune suppression in patients with ovarian cancer,overcome the occurrence of tumor immune escape,thereby increasing the overall survival rate.This experiment will study the effects of AO-I on the expression of PD-1,PD-L1,TDO mRNA in human ovarian cancer cells.Methods:Testing the inhibitory effects of AO-I on human ovarian cancer cells SKOV-3and A2780 by using RT-PCR to detect SKOV-3 and A2780 cells PD-1,PD-L1,TDO mRNA expression after the effects of AO-I with 50mmol/L concentrations at 2h and6 h time.Results:Our study found that SKOV-3 and A2780 does not have high expression of PD-1,and SKOV-3 and A2780 have high expression of PD-L1、TDO.AO-I could significantly inhibit the expression of PD-L1 and TDO mRNA in the SKOV-3 and A2780 cells,and the inhibitory activity increasing with drug concentration and the time enhancement;Conclusion:The over expression of PD-L1 in human ovarian cancer cells may be related to the immune escape of ovarian cancer.Atractylenolide I could inhibit the transcription of PD-L1 mRNA,and the inhibitory effect was positively correlated with the time of action.Atractylenolide I can down-regulate the expression of TDO mRNA,which may be related to the presence or absence of Ah R expression in SKOV-3 and A2780 cells.Atractylenolide I may improve the immunosuppressive state of ovarian cancer,inhibit the immune escape of ovarian cancer,and may improve the prognosis of the ovary.