The new metformin derivative HL156A prevents oral cancer progression by inhibiting the IGF/Akt/mTOR pathways

Summary

Metformin is a biguanide widely prescribed as an antidiabetic drug for type 2 diabetes mellitus patients. The purpose of this study was to observe the effects of the new metformin derivative, HL156A, on human oral cancer cell and to investigate its possible mechanisms. It was observed that HL156A significantly decreased FaDu and YD-10B cell viability and colony formation in a dose dependent manner. HL156A also markedly reduced wound closure and migration of FaDu and YD-10B cells. We observed that HL156A decreased mitochondrial membrane potential and induced ROS levels and apoptotic cells with caspase-3 and -9 activation. HL156A inhibited the expression and activation of IGF-1 and its downstream proteins, AKT, mTOR, and ERK1/2. In addition, HL156A activated AMPK-NF-κB signaling of FaDu and YD-10B cells. A xenograft mouse model further revealed that HL156A suppressed AT84 mouse oral tumor growth, accompanied by downregulated p-IGF-1, p-mTOR, PCNA and promoted p-AMPK and TUNEL expression. These results suggest the potential value of the new metformin derivative HL156A as a candidate for a therapeutic modality for the treatment of oral cancer.

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