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01-11-2016 | Original Article

JD enhances the anti-tumour effects of low-dose paclitaxel on gastric cancer MKN45 cells both in vitro and in vivo

Authors: Cong Wang, Ran Wang, Kairui Zhou, Saiqi Wang, Junwei Wang, Hongge Shi, Yinhui Dou, Dongxiao Yang, Liming Chang, Xiaoli Shi, Ying Liu, Xiaowei Xu, Xiujuan Zhang, Yu Ke, Hongmin Liu

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2016

Abstract

Background

Gastric cancer is the third most common cause of cancer mortality worldwide, and paclitaxel (PTX) is one of the most widely used traditional drugs in gastric cancer therapy. However, the response to traditional therapy is limited by acquired chemo-resistance and side effects. Here, we establish a newly designed combination therapy consisting of a compound that is a structural variant of oridonin, i.e. Jesridonin (JD), and low-dose PTX for gastric cancer cells (MKN45) to investigate whether the anti-tumour activity of low-dose PTX could be enhanced when combined with JD.

Methods

The interaction of JD and low-dose PTX was detected in MKN45 cells using the median-effect analysis method. The synergistic effect on cell viability and apoptosis was measured by MTT assay, colony formation assay, transient transfection, flow cytometry and Western blotting. The synergistic in vivo effect of JD plus low-dose PTX was evaluated in nude mouse xenograft models using H&E and TUNEL staining and Western blotting.

Results

JD plus low-dose PTX showed a synergistic effect, as the combination indexes were less than 1. Additionally, a synergistic anti-proliferative and pro-apoptotic effect was detected for the combination of JD and low-dose PTX. The apoptotic mechanism induced by JD plus PTX revealed that the combination therapy synergistically activated the mitochondrial pathway.

Conclusion

Our findings suggest that JD enhances the anti-tumour effect of low-dose PTX on gastric carcinoma cancer cells in both vitro and in vivo, accompanied by activation of the mitochondrial pathway, which may present a more effective therapeutic strategy in gastric cancer treatment.

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Title: JD enhances the anti-tumour effects of low-dose paclitaxel on gastric cancer MKN45 cells both in vitro and in vivo
Authors: Cong Wang
Ran Wang
Kairui Zhou
Saiqi Wang
Junwei Wang
Hongge Shi
Yinhui Dou
Dongxiao Yang
Liming Chang
Xiaoli Shi
Ying Liu
Xiaowei Xu
Xiujuan Zhang
Yu Ke
Hongmin Liu
Publication date: 01-11-2016
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 5/2016
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-016-3149-9

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