Inhibition of Autophagy Promotes the Anti-Tumor Effect of Metformin in Oral Squamous Cell Carcinoma

SIMPLE SUMMARY: In this study, we found that metformin could inhibit the cell proliferation of Oral Squamous Cell Carcinoma (OSCC) by promoting apoptosis and blocking the cell cycle. Furthermore, inhibiting autophagy with hydroxychloroquine (HCQ) could enhance the anti-tumor effect of metformin in OSCC. ABSTRACT: Oral Squamous Cell Carcinoma (OSCC) is the most common malignant tumor in the head and neck. Due to its high malignancy and easy recurrence, the five-year survival rate is only 50–60%. Currently, commonly used chemotherapy drugs for OSCC include cisplatin, paclitaxel, and fluorouracil, which are highly cytotoxic and cause drug resistance in patients. Therefore, a safe and effective treatment strategy for OSCC is urgent. To address this issue, our study investigated the anti-tumor activity of metformin (the first-line diabetes drug) in OSCC. We found that metformin could inhibit OSCC cell proliferation by promoting apoptosis and blocking the cell cycle in G1 phase. Additionally, we also found that metformin could induce protective autophagy of OSCC cells. After inhibiting autophagy with hydroxychloroquine (HCQ), the metformin-induced apoptosis was enhanced. In vitro, metformin inhibited the growth of subcutaneous xenograft tumor in nude mice and HCQ enhanced this effect of metformin. Therefore, metformin combined with HCQ may become a safe and effective treatment strategy for OSCC.