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

BMC Cancer

Zhi-Ming Shao³  Da-Li Hu¹  Qi Hong³  Yi-Feng Hou³  Zhe-Bin Liu³  Wen-Huan Xu² 

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

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

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

关键词: Breast cancer;    IRE1;    Autophagy;    ER stress;    PA-MSHA;   

Others  :  858884
DOI  :  10.1186/1471-2407-14-273

 received in 2013-07-23, accepted in 2014-03-11,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Xu et al.; licensee BioMed Central Ltd.

【 图 表 】

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