GMI ablates cancer stemness and cisplatin resistance in oral carcinomas stem cells through IL-6/Stat3 signaling inhibition
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Tung Yuan Wang1,*, Cheng-Chia Yu1,2,3,*, Pei-Ling Hsieh3, Yi-Wen Liao1, Chuan-Hang Yu1,2 and Ming-Yung Chou1,2
1School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
2Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
3Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
*These authors have contributed equally to this work
Ming-Yung Chou, email: [email protected]
Chuan-Hang Yu, email: [email protected]
Keywords: oral squamous cell carcinomas, immunomodulatory protein GMI, cancer stem cells, chemoresistance, IL-6/Stat3 signaling
Received: May 04, 2017 Accepted: June 19, 2017 Published: July 31, 2017
Cancer stem cells (CSCs) have been identified to exert tumor-initiating ability, resulting in the recurrence, metastasis and chemoresistance of oral squamous cell carcinomas. In the present study, we showed that GMI, an immunomodulatory protein from Ganoderma microsporum, induc ed a cytotoxic effect in oral carcinomas stem cells (OCSCs). Treatment of GMI dose-dependently inhibited the expression of CSC markers, including ALDH1 activity and CD44 positivity. Moreover, GMI suppressed the self-renewal property, colony formation, migration, and invasion abilities as well as potentiated chemo-sensitivity in OCSCs. Our results suggested that the tumor suppressive effect of GMI was mediated through inhibition of IL-6/Stat3 signaling pathway. Furthermore, tumor growth was reduced in mice bearing xenograft tumors after oral administration of GMI. Taken together, we demonstrated the anti-CSC effect of GMI in oral cancer and GMI may serve as a natural cisplatin adjuvant to prevent cancer recurrence.
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