J Cancer 2016; 7(9):1133-1141. doi:10.7150/jca.14519
Proteasome Inhibitor YSY01A Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant Human Ovarian Cancer Cells
1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
2. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
3. Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, China
4. Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China
* W. H and Q. Z. contributed equally to this work.
Huang W, Zhou Q, Yuan X, Ge Zm, Ran Fx, Yang Hy, Qiang Gl, Li Rt, Cui Jr. Proteasome Inhibitor YSY01A Enhances Cisplatin Cytotoxicity in Cisplatin-Resistant Human Ovarian Cancer Cells. J Cancer 2016; 7(9):1133-1141. doi:10.7150/jca.14519. Available from http://www.jcancer.org/v07p1133.htm
Cisplatin is one of the most common drugs used for treatment of solid tumors such as ovarian cancer. Unfortunately, the development of resistance against this cytotoxic agent limits its clinical use. Here we report that YSY01A, a novel proteasome inhibitor, is capable of suppressing survival of cisplatin-resistant ovarian cancer cells by inducing apoptosis. And YSY01A treatment enhances the cytotoxicity of cisplatin in drug-resistant ovarian cancer cells. Specifically, YSY01A abrogates regulatory proteins important for cell proliferation and anti-apoptosis including NF-κB p65 and STAT3, resulting in down-regulation of Bcl-2. A dramatic increase in cisplatin uptake was also observed by inductively coupled plasma-mass spectrometry following exposure to YSY01A. Taken together, YSY01A serves as a potential candidate for further development as anticancer therapeutics targeting the proteasome.
Keywords: proteasome inhibitor, YSY01A, ovarian cancer, cisplatin resistance, apoptosis, NF-κB and STAT3