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Open Access 01-12-2018 | Original Article

Oleandrin synergizes with cisplatin in human osteosarcoma cells by enhancing cell apoptosis through activation of the p38 MAPK signaling pathway

Authors: Lei Yong, Yunlong Ma, Bin Zhu, Xiao Liu, Peng Wang, Chen Liang, Guanping He, Zhigang Zhao, Zhongjun Liu, Xiaoguang Liu

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2018

Abstract

Purpose

Our previous studies have reported the antitumor effect of oleandrin on osteosarcoma; however, its chemosensitizing effect in osteosarcoma treatment is still unknown. Therefore, we explored the sensitizing effects of oleandrin to cisplatin in osteosarcoma and investigated the potential mechanisms.

Methods

After exposure to oleandrin and/or cisplatin, CCK-8 and colony formation assays, DAPI staining and flow cytometry were performed to detect cell proliferation and apoptosis in 143B, U-2OS and MG-63 osteosarcoma cells. The median-effect analysis was applied to evaluate the combined effect. Western blot was used to determine the expression of related proteins. Osteosarcoma xenografts and histological observations were applied to confirm the combined effect in vivo.

Results

Compared with cisplatin or oleandrin alone, the combined treatment significantly inhibited cell proliferation and induced cell apoptosis. The median-effect analysis indicated a synergistic cytotoxic effect. The combined treatment downregulated Bcl-2 and upregulated Bax and cleaved caspase-3, -8 and -9. And the suppression of caspases reduced cell death. Furthermore, oleandrin alone or with cisplatin, activated the p38 MAPK/Elk-1 pathway. The inhibition of the p38 MAPK pathway increased cell viability and reduced apoptosis. In vivo, the combined treatment was also verified to significantly inhibit tumor growth, induce apoptosis and activate the p38 MAPK pathway.

Conclusions

The combination of oleandrin with cisplatin exerts a synergistic antitumor effect in osteosarcoma, which relates to the activation of the p38 MAPK pathway.

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Title: Oleandrin synergizes with cisplatin in human osteosarcoma cells by enhancing cell apoptosis through activation of the p38 MAPK signaling pathway
Authors: Lei Yong
Yunlong Ma
Bin Zhu
Xiao Liu
Peng Wang
Chen Liang
Guanping He
Zhigang Zhao
Zhongjun Liu
Xiaoguang Liu
Publication date: 01-12-2018
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2018
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-018-3692-7

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Abstract

Purpose

Methods

Results

Conclusions

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