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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and the majority of HNSCC is oral squamous cell carcinoma (OSCC) [1]
We showed that GMI, an immunomodulatory protein from Ganoderma microsporum, induc ed a cytotoxic effect in oral carcinomas stem cells (OCSCs)
We first investigated the cell survival of these two OCSCs derived from oral cancer cell lines and normal human gingival epithelioid cell line (SG) in order to understand the cytotoxicity of GMI
Summary
Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and the majority of HNSCC is oral squamous cell carcinoma (OSCC) [1]. There has been substantial progress in cancer treatment, survival rates have improved only frugally over the past few decades [2]. A significant number of patients still suffer from recurrent cancer after chemotherapy [3]. It has been shown that 3-year overall survival rate of advanced OSCC patients with recurrence was less than 30% [4]. Accumulating evidence has suggested that the resistance of radiochemotherapy is attributed to the cancer stem cells (CSCs) within the heterogeneous tumor mass [5].
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