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Oncotarget. 2017 Jul 31;8(41):70422-70430. doi: 10.18632/oncotarget.19711. eCollection 2017 Sep 19.

GMI ablates cancer stemness and cisplatin resistance in oral carcinomas stem cells through IL-6/Stat3 signaling inhibition.

Author information

1
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
2
Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
3
Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.

Abstract

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.

KEYWORDS:

IL-6/Stat3 signaling; cancer stem cells; chemoresistance; immunomodulatory protein GMI; oral squamous cell carcinomas

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