J Cancer 2020; 11(19):5568-5577. doi:10.7150/jca.41115

Research Paper

Gambogic acid affects ESCC progression through regulation of PI3K/AKT/mTOR signal pathway

Jiarui Yu2#, Wei Wang2#, Weinan Yao2, Zhao Yang2, Peng Gao2, Meiyue Liu2, Huan Wang2, Siyuan Chen2, Dan Wang2, weixi Wang2✉, Guogui Sun1,2✉

1. School of Clinical Medicine, Affiliated Hospital, School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063000, China.
2. Department of Radiation Oncology, North China University of Science and Technology Affiliated People's Hospital, Tangshan, Hebei 063000, China.
#These authors contributed equally to this work.

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Yu J, Wang W, Yao W, Yang Z, Gao P, Liu M, Wang H, Chen S, Wang D, Wang w, Sun G. Gambogic acid affects ESCC progression through regulation of PI3K/AKT/mTOR signal pathway. J Cancer 2020; 11(19):5568-5577. doi:10.7150/jca.41115. Available from http://www.jcancer.org/v11p5568.htm

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Esophageal squamous cell carcinoma (ESCC) is an invasive gastrointestinal malignancy and in urgent need of new effective therapies. Gambogic acid (GA) exhibits anti-cancer effects in many cancer cells, but it remains to be determined whether GA has the same effect on ESCC. Here, we reported that GA treatment caused an inhibition in ESCC cell proliferation, migration and invasion. Meanwhile, GA induced dose-dependent apoptosis of ESCC cells, repressed the expression of Bcl2 and up-regulated the levels of Bax protein, cleaved-PARP1 and cleaved-caspase 3/9. Further investigation showed that GA down-regulated the levels of PI3K, p-AKT and p-mTOR, while promoted PTEN expression in ESCC cells. Taken together, we provided the first demonstration that GA exerts anti-tumor effects on ESCC cells presumably through regulating PTEN-PI3K-AKT-mTORpathway, suggestive of a therapeutic potential for ESCC.

Keywords: ESCC, Gambogic acid, Proliferation, Apoptosis, PI3K/AKT/mTOR