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Open Access Highly Accessed Research article

Inhibition of autophagy enhances the cytotoxic effect of PA-MSHA in breast cancer

Wen-Huan Xu1234, Zhe-Bin Liu123, Yi-Feng Hou123, Qi Hong123, Da-Li Hu5 and Zhi-Ming Shao123*

Author Affiliations

1 Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China

2 Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China

3 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China

4 Department of Oncology, Wuxi No. 4 People’s Hospital, Affiliated Hospital of Jiangnan University, 214062 Wuxi, Jiangsu, P.R. China

5 Research and medical Department, Beijing Wanter Bio-pharmaceutical Co., Ltd, Beijing Huairou Yanqi Economic Technical Department Area, Beijing 101407, P.R. China

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BMC Cancer 2014, 14:273  doi:10.1186/1471-2407-14-273

Published: 21 April 2014

Abstract

Background

PA-MSHA, a genetically engineered Pseudomonas aeruginosa (PA) strain, is currently under investigation as a new anti-cancer drug. It can induce cell cycle arrest and apoptosis in different human cancer cells, including hormone receptor negative breast cancer cells. However, the underlying mechanism of tumor lethality mediated by PA-MSHA remains to be fully investigated.

Methods

The effect of PA-MSHA on human hormone receptor negative breast cancer cells was analyzed by morphological measurement, western blot, cell proliferation assay and mouse xenograft model.

Results

PA-MSHA was found to induce endoplasmic reticulum (ER) stress in breast cancer cell lines through the IRE1 signaling pathway. Inhibiting autophagy potentiated the cytotoxic effect of PA-MSHA while treating breast cancer cell lines. In mouse xenograft model, PA-MSHA produced more pronounced tumor suppression in mice inoculated with IRE1 gene knockdown. MDA-MB-231HM cells.

Conclusions

These findings demonstrated inhibiting autophagy together with PA-MSHA might be a promising therapeutic strategy in treating hormone receptor negative breast cancer cells.

Keywords:
PA-MSHA; ER stress; Autophagy; IRE1; Breast cancer