Berberine inhibits EGFR signaling and enhances the antitumor effects of EGFR inhibitors in gastric cancer
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Junxiong Wang1, Shuo Yang2, Xiqiang Cai3, Jiaqiang Dong3, Zhangqian Chen3, Rui Wang3, Song Zhang3, Haichao Cao3, Di Lu1, Tong Jin1, Yongzhan Nie3, Jianyu Hao1, Daiming Fan1,3
1Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
2Department of Laboratory Medicine, Peking University Third Hospital, Beijing 100191, China
3State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
Daiming Fan, email: firstname.lastname@example.org
Jianyu Hao, email: email@example.com
Yongzhan Nie, email: firstname.lastname@example.org
Keywords: gastric cancer, berberine, EGFR, cetuximab, STAT3
Received: April 23, 2016 Accepted: September 20, 2016 Published: October 12, 2016
Cetuximab plus chemotherapy for advanced gastric cancer (GC) shows an active result in phase 2 trials. Unfortunately, Combination of cetuximab does not provide enough benefit to chemotherapy alone in phase 3 trials. Studies have demonstrated that berberine can suppress the activation of EGFR in tumors. In this study, we evaluated whether berberine could enhance the effects of EGFR-TKIs in GC cell lines and xenograft models. Our data suggest that berberine could effectively enhance the activity of erlotinib and cetuximab in vitro and in vivo. Berberine was found to inhibit growth in GC cell lines and to induce apoptosis. These effects were linked to inhibition of EGFR signaling activation, including the phosphorylation of STAT3. The expressions of Bcl-xL and Cyclind1 proteins were decreased, whereas the levels of cleavage of poly-ADP ribose polymerase (PARP) were considerably increased in the cell lines in response to berberine treatment. These results suggest a potential role for berberine in the treatment of GC, particularly in combination with EGFR-TKIs therapy. Berberine may be a competent therapeutic agent in GC where it can enhance the effects of EGFR inhibitors.
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