iTRAQ-based quantitative proteomic analysis of the inhibition of cervical cancer cell invasion and migration by metformin.

ABSTRACT

In recent years the anti-diabetic drug metformin has been shown to inhibit tumor growth, but the underlying mechanism is unclear. Our previous results showed that metformin can destroy the sponge effect of long-chain non-coding RNA MALAT1/miR-142-3p and inhibit the proliferation of cervical cancer cells. Metformin can inhibit the PI3K/Akt signaling pathway and synergizes with Nelfinavir to inhibit the proliferation and invasion of cervical cancer cells. In this study, we used iTRAQ-based proteomics, mass spectrometry-based targeted proteomics, immunoblotting, and bioinformatics to analyze the molecular mechanism by which metformin inhibits the proliferation and invasion of cervical cancer cells. We found that 53 proteins were differentially expressed in cervical cancer cells after metformin treatment, of which 20 were up-regulated and 33 were down-regulated. Bioinformatics analysis showed that the 53 differentially expressed proteins are negative regulators of receptor signaling that inhibit cell growth and are mainly enriched in cell growth and apoptosis signaling pathways. We performed PRM verification on 11 of the differentially expressed proteins and found that they were all associated with apoptosis. We also found that metformin up-regulated the expression of the tumor suppressor IGFBP7 to inhibit the proliferation and invasion of cervical cancer cells. Our results indicate that metformin mainly regulates the insulin signaling pathway and interferes with cell proliferation and apoptosis to inhibit proliferation and invasion of cervical cancer cells. These differentially expressed proteins may become new targets for the treatment of cervical cancer.