J Cancer 2018; 9(6):1050-1056. doi:10.7150/jca.23388

Research Paper

Autophagy Inhibition Stimulates Apoptosis in Oesophageal Squamous Cell Carcinoma Treated with Fasudil

Fa-Jun Xie1,2✉*, Qiu-Qing Zheng2,3*, Jing Qin1,2, Ling-Ling Zhang4, Na Han1,2, Wei-Min Mao2,5✉

1. Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.
2. Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Oesophagus), Hangzhou 310022, China.
3. Department of Ultrasonography, Zhejiang Cancer Hospital, Hangzhou 310022, China.
4. Department of Medical Oncology, Peking University International Hospital, Beijing 102206, China.
5. Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, China.
*These authors contributed equally to this work.

Abstract

Fasudil has been proven to be a promising chemotherapeutic drug for various malignancies. However, the potential anticancer effects of fasudil in oesophageal squamous cell carcinoma (ESCC) remain to be established. We confirmed the RhoA activity is inhibited by fasudil in ESCC cells. Then measured the effects of fasudil on apoptosis and autophagy in ESCC. Our study showed fasudil could both induce ESCCs apoptosis and autophagy, and when fasudil-induced autophagy was inhibited by knockdown of the essential autophagy genes (Beclin 1 or ATG7), and pharmacologic agent (chloroquine) treatment, both treatments also significantly sensitized ESCC to fasudil-induced apoptosis, reducing cell viability in vitro. Our study showed autophagy inhibitors combined with fasudil could significantly induce ESCC apoptosis, which may provide a novel therapeutic strategy for ESCC.

Keywords: Fasudil, Oesophageal squamous cell carcinoma, Apoptosis, Autophagy

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How to cite this article:
Xie FJ, Zheng QQ, Qin J, Zhang LL, Han N, Mao WM. Autophagy Inhibition Stimulates Apoptosis in Oesophageal Squamous Cell Carcinoma Treated with Fasudil. J Cancer 2018; 9(6):1050-1056. doi:10.7150/jca.23388. Available from http://www.jcancer.org/v09p1050.htm