TRAIL与卡铂联合诱导卵巢癌细胞凋亡的研究

目的探讨肿瘤坏死因子相关凋亡诱导配体（TRAIL）与卡铂（CBP）联合应用对体外培养的卵巢A2780细胞的生物学效应及其作用机制。方法采用MTT法、流式细胞术，检测体外培养的A2780细胞在卡铂和TRAIL共同作用下的细胞增殖抑制效应以及细胞凋亡程度，应用半定量逆转录多聚酶链反应（RT-PCR）法检测TRAIL受体的mRNA表达水平。结果A2780细胞对TRAIL敏感，TRAIL与卡铂联合用药对细胞的增殖抑制呈现高效协同作用，与单独用药组比较有显著性差异（P〈0．05）；流式细胞术分析协同性杀伤作用主要由于TRAIL和CBP联合诱导细胞凋亡引起；RT—PCR法检测结果显示A2780细胞在TRAIL与卡铂联合用药后均表现死亡受体DR4、DR5表达水平上调和诱骗受体DcR1、DcR2表达水平下调。结论在体外TRAIL与化疗药物联用能明显抑制肿瘤细胞增殖，诱导肿瘤细胞凋亡，卡铂能明显增强TRAIL对肿瘤细胞的敏感性，其诱导机制可能与死亡受体DR4、DR5表达水平上调和诱骗受体DcR1、DcR2表达水平下调相关。

Combined Effects of Tumor Necrosis Factor-related Apoptosis-inducing Ligand and Chemotherapeutic Drug in Inducing Apoptosis of Ovarian Cancer Cell

Objective To investigate the combined effects of tumor necrosis factor-related apoptosis-inducing liand(Apo2L/TRAIL) with Carboplatin(CBP) on ovarian cancer cell line A2780 and its mechanism.Methods With the treatment of TRAIL and CBP,the cytotoxic effect and the apoptosis propotion were measured by MTT(micoculture tetrazolium dye) assay and Flow Cytometry.The expression of TRAIL receptor mRNA was assayed by semiquantitive RT-PCR.Results A2780 was sensitive to TRAIL.CBP had a synergistic inhibitory effect with TRAIL on the growth of the A2780 cell(P<0.05).FCM revealed that CBP could enhance TRAIL-induced apoptosis of cancer cell line A2780.The expression of DR4 and DR5 was significantly higher in A2780 with combined treatment of TRAIL and CBP than in those with TRAIL or CBP alone,while the expression of DcR1 and DcR2 was markedly decreased(P<0.05) in A2780 with TRAIL+CBP.Conclusion In vitro,CBP and TRAIL can inhibit the growth of A2780 cell line and induce cell apoptosis.The mechanism may correlate with the up-regulation of DR4 and DR5 and down-regulation of DcR1 and DcR2.