Synergistic effects of the sesquiterpene lactone, EPD, with cisplatin and paclitaxel in ovarian cancer cells

Journal of Experimental & Clinical Cancer Research

Tom van Wezel²  Baptist JMZ Trimbos¹  Jaap DH van Eendenburg²  Willem E Corver²  Arnoud Boot²  Caroline van Haaften¹ 

[1] Department of Gynecology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands;Department of Pathology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands

关键词: Synergism;    Paclitaxel;    Cisplatin;    EPD;    Ovarian cancer;   

Others  :  1219936
DOI  :  10.1186/s13046-015-0157-2

 received in 2014-09-29, accepted in 2015-04-09,  发布年份 2015

【 摘 要 】

Background

Ovarian cancer remains still the leading cause of death of gynecological malignancy, in spite of first-line chemotherapy with cisplatin and paclitaxel. Although initial response is favorably, relapses are common and prognosis for women with advanced disease stays poor. Therefore efficacious approaches are needed.

Methods

Previously, an anti-cancer agent, EPD exhibited potent cytotoxic effects towards ovarian cancer and not towards normal cells. Cell viability and cell cycle analysis studies were performed with EPD, in combination with cisplatin and/or paclitaxel, using the ovarian carcinoma cell lines: SK-OV-3, OVCAR-3, JC, JC-pl and normal fibroblasts. Cell viability was measured using Presto Blue and cell cycle analysis using a flow cytometer. Apoptosis was measured in JC and JC-pl , using the caspase 3 assay kit.

Results

In JC-pl, SK-OV-3 and JC, synergistic interactions between either EPD and cisplatin or EPD and paclitaxel were observed. For the first time the effects of EPD on the cell cycle of ovarian cancer cells and normal cells was studied. EPD and combinations of EPD with cisplatin and/ or paclitaxel showed cell cycle arrest in the G ₂ /M phase. The combination of EPD and cisplatin showed a significant synergistic effect in cell line JC-pl, while EPD with paclitaxel showed synergistic interaction in JC. Additionally, synergistic drug combinations showed increased apoptosis.

Conclusions

Our results showed a synergistic effect of EPD and cisplatin in an ovarian drug resistant cell line as well as a synergistic effect of EPD and paclitaxel in two other ovarian cell lines. These results might enhance clinical efficacy, compared to the existing regimen of paclitaxel and cisplatin.

【 授权许可】

   
2015 van Haaften et al.

【 图 表 】

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