Berberine-targeted miR-21 chemosensitizes oral carcinomas stem cells
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Che-Yi Lin1, Pei-Ling Hsieh2,*, Yi-Wen Liao3,*, Chih-Yu Peng3, Ming-Yi Lu3, Ching-Hsuan Yang2, Cheng-Chia Yu2,3,4 and Chia-Ming Liu3,4
1Department of Oral and Maxillofacial Surgery, Chi Mei Hospital, Tainan, Taiwan
2Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
3School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
4Department of Dentistry, Chung Shan Medical University, Taichung, Taiwan
*These authors have contributed equally to this work
Cheng-Chia Yu, email: [email protected]
Chia-Ming Liu, email: [email protected]
Keywords: oral squamous cell carcinomas, miR-21, berberine
Received: June 16, 2017 Accepted: August 04, 2017 Published: September 08, 2017
Cancer recurrence and chemoresistance are two major obstacles to the treatment of oral squamous cell carcinomas (OSCC). And cancer stem cells (CSCs) have been found to possess tumor initiating, self-renewal and metastasis abilities, resulting in the relapse and chemoresistance of OSCC. In the present study, we investigated the anti-CSCs effect of berberine, a phenanthrene alkaloid isolated from the Berberis genus. Our results demonstrated that berberine dose dependently downregulated the oncogenicity in vitro, including ALDH1 activity, self-renewal property, and colony formation and invasion abilities as well as potentiated chemosensitivity of OSCC-CSCs. In addition, tumor growth in mice was attenuated after oral gavage treatment of berberine. We showed that the expression of miR-21 was suppressed following administration of berberine in OSCC-CSCs. And inhibition of endogenous miR-21 reduced the characteristics of CSCs, including self-renewal, migration, invasion capabilities and ALDH1 activity. Taken together, we demonstrated the anti-CSC effect of berberine in oral cancer and its potential to serve as adjuvant to traditional chemotherapy to improve treatment effect.
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