RAPAMYCIN ON THE TREATMENT OF MUCOEPIDERMOID CARCINOMAS AND SQUAMOUS CELL CARCINOMAS

Mucoepidermoid carcinomas (MEC) are the most common malignancy of the salivary glands. Dysfunctional clock signaling is observed in a variety of pathologic conditions. Members of the clock gene family are upregulated in tumor cells. We explored the role of the mTOR signaling pathway, commonly found upregulated in tumors including in MEC, oral squamous cell carcinomas (OSCC), and its population of cancer stem cells (CSC). We also explored the potential implication on the disruption of the mTOR signaling on the expression the clock gene family member BMAL1 in tumor behavior using the specific mTOR inhibitor rapamycin. We showed that MEC and HNSCC are endowed with high expression levels of mTOR and BMAL1. Rapamycin demonstrates potent antiproliferative activity in MEC and HNSCC cells, with the ability to reduce tumor invasion and migration. We also found that rapamycin is an effective modulator of the core clock gene BMAL1. Unexpectedly, inhibition of mTOR signaling resulted in the proliferation of CSC in HNSCC while reduced CSC from MEC. These findings suggest rapamycin have different effects on CSC of different solid tumors. While administration of rapamycin was efficient in treating MEC tumors and depleting its CSC, rapamycin failed in disrupting the population of CSC from OSCC.