Cisplatin-mediated sensitivity to TRAIL-induced cell death in human granulosa tumor cells

Gynecologic Oncology
Dori C WoodsA L Johnson

Abstract

The goal of the present study was to determine the efficacy of combinatorial treatment using cisplatin and tumor necrosis factor-related apoptosis including ligand (TRAIL) to promote apoptosis in granulosa cell tumor (GCT) lines, in vitro. Two human GCT lines (COV434 and KGN) were treated with cisplatin or TRAIL, alone or in combination. The cytotoxic effects of each treatment were evaluated using a methyl tetrazolium salt (MTS) assay. Initiation of TRAIL-induced apoptosis was verified by PARP- and FLIP-cleavage. Overexpression and knockdown studies were conducted to evaluate the role of p53 in TRAIL-induced cell death. Real-time PCR was used for gene expression analysis of the TRAIL receptor dr5 and the pro-apoptotic bax following treatment with cisplatin. Treatment with TRAIL (100-200 ng/ml) led to a slight, but significant, loss of cell viability following an 18-h culture. This effect was enhanced following pre-treatment with cisplatin (25 microM) for 2 or 18 h. Moreover, pre-treatment with cisplatin decreased the maximal effective dose of TRAIL from 100 ng/ml to as low as 3 ng/ml in both cell lines. GCT lines overexpressing or deficient in p53 were used to determine the requirement for p53 on TRAIL-induced apoptosis. While ...Continue Reading

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Citations

Feb 10, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Pengyuan LiuMing You
Jan 19, 2013·Cellular and Molecular Life Sciences : CMLS·Nor Saadah M Azahri, Mary M Kavurma
Jul 20, 2010·Gynecologic Oncology·Kerri S BevisJ Michael Straughn
Mar 14, 2009·Differentiation; Research in Biological Diversity·M JääskeläinenT E Vaskivuo
Mar 3, 2009·Transplantation Proceedings·M TanemuraT Ito
Jul 14, 2010·The Australian & New Zealand Journal of Obstetrics & Gynaecology·Puliyath Geetha, M Krishnan Nair
Sep 28, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Jinbong ParkJae-Young Um
May 28, 2011·Biochemical and Biophysical Research Communications·Dori C WoodsA L Johnson
Oct 27, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Anniina FärkkiläMarkku Heikinheimo
Aug 16, 2012·Cancer Biology & Therapy·Joshua E Allen, Wafik S El-Deiry
Jun 13, 2008·Nature Protocols·Thomas D Schmittgen, Kenneth J Livak

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