Research Of Conbination Effects Tumor Ecrosis Factor-Related Apoptosis-Inducing Ligand And Chemotherapetic Drug Inducing Ovarian Neoplasms Apoptosis

Objective: Tumor necrosis factor related apoptosis inducing ligand(TRAIL) or APO-2 ligand(APO-2L) was a member of tumor necrosis factor(TNF) family found recently.TRAIL and it's receptors could induce cell apoptosis, kill tumour cells and transformant cells.Especially,TRAIL has no lethal effect on normal tissues and cells.Intensity modulated radiation therapy and chemotherapy cause TRAIL potential application on tumor therapy aspects.This experiment investigated the effects of combination of TRAIL and Carboplatin on ovarian cancer cell strain A2780 and the intracellular regulation of TRAIL-mediated apoptosis in vitro to provide new clinical treatment channels.Methods: Human ovarian cancer cell strain-A2780 was cultured in vitro.The cytotoxic effects were measured by MTT(methyl thiazolyl tetrazolium) assay;the apoptosis propotions among these cells were determined by Flow Cytometry.The expressions of TRAIL receptors were assayed by reverse transcription polymerase chain reaction(RT-PCR) in ovarian cancer cell with or without TRAIL and Carboplatin.Results:1 , Ovarian cancer cell strain A2780 was sensitive to TRAIL by MTT assay.The cells were comparatively more responsive than no Carboplatin or no TRAIL(P<0.01). The synergistic effects presented by combination of TRAIL and Carboplatin were significantly higher than TRAIL or Carboplatin used alone on the A2780 cell strain(P<0.05);2> The cytotoxicity was mainly attributed to cell apoptosis by flow cytometry assay (FCM).The synergistic effects origin from apoptosis that combination of TRAIL and Carboplatin induced. The concentration of TRAIL lOOng/ml could induce apoptosis,and the apoptosis rate is 40.96%;While together with Carboplatin 10ng/ml,the apoptosis rate is up to 71.40%.The apoptosis effects presented by combination were significantly higher than TRAIL or Carboplatin used alone on the A2780 cell strain(/><0.01);3^ The RT-PCR reavealed that the expressions of DR4 and DR5 on ovarian cancer cell strain A2780 with combination TRAIL and Carboplatin were significantly higher than with TRAIL or Carboplatin alone(P<0.05);and the expressions of DcRl and DcR2 were no difference(/)>0.05).Conclusions:1 n In vitro, TRAIL could inhibit the growth of ovarian cancer cell strain A2780.The effects of Carboplatin could be increased with TRAIL,which provided a new way for therapy of ovarian cancer;2^ The synergistic effects that combination of TRAIL and Carboplatin presented were significantly higher than TRAIL or Carboplatin used alone on the ovarian cancer cell strain A2780;3> The mechanism of combination effects that TRAIL and chemotherapetic drug-Carboplatin induce ovarian cancer cell strain A2780 apoptosis is correlated with the up-regulation DR4 and DR5.