Effect of recombinant human TRAIL protein combined with cisplatin on the growth and apoptosis of human ovarian cancer cells

冯　忻; 王彩霞; 欧志英

doi:10.19401/j.cnki.1007-3639.2016.08.002

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Effect of recombinant human TRAIL protein combined with cisplatin on the growth and apoptosis of human ovarian cancer cells

更新时间：2025-12-31

- Effect of recombinant human TRAIL protein combined with cisplatin on the growth and apoptosis of human ovarian cancer cells
- China Oncology Vol. 26, Issue 8, Pages: 648-654(2016)
- 作者机构：
  
  1. 南方医科大学中西医结合医院，南方医科大学中西医结合肿瘤中心,广东,广州,510310
  2. 广州市妇女儿童医疗中心,广东,广州,510623
  3. 武警广东总队医院妇产科,广东,广州,510507
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2016.08.002
  CLC：
- Published Online：19 October 2016，
  
  Published：19 October 2016
- 稿件说明：
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冯　忻,王彩霞,欧志英. 重组人TRAIL蛋白联合顺铂对人卵巢癌细胞生长及凋亡的影响[J]. 中国癌症杂志, 2016, 26(8): 648-654.

冯　忻, 王彩霞, 欧志英. Effect of recombinant human TRAIL protein combined with cisplatin on the growth and apoptosis of human ovarian cancer cells[J]. China Oncology, 2016, 26(8): 648-654.
冯　忻,王彩霞,欧志英. 重组人TRAIL蛋白联合顺铂对人卵巢癌细胞生长及凋亡的影响[J]. 中国癌症杂志, 2016, 26(8): 648-654. DOI： 10.19401/j.cnki.1007-3639.2016.08.002.

冯　忻, 王彩霞, 欧志英. Effect of recombinant human TRAIL protein combined with cisplatin on the growth and apoptosis of human ovarian cancer cells[J]. China Oncology, 2016, 26(8): 648-654. DOI： 10.19401/j.cnki.1007-3639.2016.08.002.

摘要

背景与目的：研究发现肿瘤坏死因子的相关凋亡诱导配体(tumor necrosis factor-related apoptosis inducing ligand，TRAIL)可以增强化疗药物对肿瘤细胞的杀伤作用。本研究旨在探讨TRAIL与顺铂联合应用对体外培养的卵巢癌细胞SKOV3和OVCAR3生长凋亡的影响及可能的诱导机制。方法：利用MTT法和流式细胞仪检测在顺铂和重组人TRAIL蛋白共同作用下，SKOV3和OVCAR3细胞的增殖抑制效应及细胞凋亡程度；并应用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction，RTFQ-PCR)检测药物处理后TRAIL死亡受体DR4、DR5的mRNA表达水平；同时用蛋白[质]印迹法(Western blot)检测DR4、DR5的蛋白表达水平。结果：SKOV3和OVCAR3细胞均对TRAIL蛋白敏感，随着TRAIL蛋白浓度的升高，细胞的生长抑制率可达64%；而TRAIL与顺铂联合用药对两种细胞的抑制率均达到92%以上，对细胞的增殖抑制呈现高效协同作用，与单独用药组比较差异有统计学意义(P0.05)；TRAIL和顺铂联合组两种细胞凋亡率分别为(31.50±0.79)%和(36.60±1.31)%，显著高于单独用药组；RTFQ-PCR和Western blot检测结果显示，SKOV3和OVCAR3细胞在TRAIL与顺铂联合用药后，死亡受体DR4、DR5表达水平均显著上调。结论：在体外，TRAIL与化疗药物顺铂联用能明显抑制卵巢癌细胞增殖，诱导肿瘤细胞凋亡。TRAIL能明显增强顺铂对卵巢癌细胞的敏感性，其诱导机制可能与死亡受体DR4、DR5表达水平上调有关。

Abstract

Background and purpose: The study has found that tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can enhance the cytotoxic effect of chemotherapeutic drugs on tumor cells. The aim of our study was to investigate the effects of the tumor TRAIL and cisplatin combined application on the growth and apoptosis of human ovarian cancer cell lines SKOV3 and OVCAR3

and the possible mechanism. Methods: Under the combined application of cisplatin and TRAIL

MTT method and flow cytometry were used to detect the proliferation and apoptosis of SKOV3 of OVCAR3 cells; the mRNA expression levels of death receptors

DR4 and DR5

were detected by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR). At the same time

the protein expression levels of DR4 and DR5 were detected by Western blot. Results: SKOV3 and OVCAR3 cells were sensitive to TRAIL protein

and with the increasing of TRAIL protein concentration

cell growth inhibitory rate up to 64%. When the combination application of TRAIL and cisplatin

the inhibition rate of the two cells reached more than 92%

and the two drugs showed high synergistic effect

compared with the single drug group (P0.05). Flowcytometry analysis indicated that the synergistic killing effect of TRAIL and cisplatin was mainly due to the cell apoptosis. RTFQ-PCR and Western blot detection results showed that the DR4 and DR5 were up-regulated under the combined application of TRAIL and cisplatin. Conclusion: In vitro

TRAIL and cisplatin combined application can significantly inhibit the proliferation of human ovarian cancer cells and induce tumor cell apoptosis. TRAIL can obviously enhance the sensitivity of cisplatin to tumor cells. The mechanism may be related to the increased death receptor DR4 and DR5 expression level.

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