GMI Impairs Cancer Stemness and chemoresistance in Oral Carcinomas Stem Cells

Objectives: Cancer stem cells (CSCs) have been identified to exert tumor initiating ability, resulting in the relapse, metastasis and chemoresistance of oral squamous cell carcinomas. As such, strategy that target CSCs may be a promising approach for OSCC.

Methods: Oralspheres was applied to isolate oral cancer stem cells (OCSC). Aldehyde dehydrogenase 1 activity and CD44 positivity of OCSC with GMI, an immunomodulatory protein from Ganoderma microsporum, treatment were assessed by flow cytometry analysis. In vitro, in vivo oncogenicity assays, and mechanistic exporation were performed to assess in OCSC with GMI treatment.
Results: In the present study, we showed that GMI, an immunomodulatory protein from Ganoderma microsporum, induced a cytotoxic effect in oral cancer stem cells (OCSCs). Treatment of GMI dose dependently down-regulated the oncogenicity, including ALDH1 activity, CD44 positivity, self-renewal property, invasion and colony formation abilities as well as potentiated chemo-sensitivity in ALDH1+CD44+ OCSCs. And the tumor suppressive effect of GMI was mediated through the inhibition of IL-6/Stat3 signaling pathway. Furthermore, tumor growth was reduced in mice bearing xenograft tumors after oral gavage treatment of GMI.
Conclusions: We demonstrated the anti-CSC effect of GMI in oral cancer and GMI may be able to serve as natural Cisplatin adjuvant to prevent cancer recurrence.