New therapies against cancer: evaluation of metformin action on programmed cell death, angiogenesis and metastasis in hepatic carcinoma

Abstract

Although advances in knowledge of the genesis and progression of cancer, and development of new antitumor drugs, mortality rates by this disease are still quite high. Thus, the application of new drugs as main or adjuvant in cancer treatment have been studied over the years, though none of these drugs had reached significant success in clinical evaluations until now. Therefore, the search for drugs that act on the hallmarks of cancer safely, for a therapeutic use, has been a key goal of many researchers in the oncology's study. This project aims to evaluate the molecular mechanism of induction in cell death on human liver carcinoma cells HepG2, as well as the possible action of metformin as an anti-metastatic and anti-angiogenic agent in this type of tumor. Actually, it is known that the use of metformin as antitumor agent is linked to its ability to inhibit the pathway PI3K/Akt/mTOR (known by its specific association with the replicative and metastatic potential of tumor cells) stimulating the activity of the protein kinase activated by AMP (AMPK), though the effects of this drug may also be independent of the modulation of AMPK. Thus, it is proposed to evaluate the action this drug on cell death induced in human liver tumor cell line HepG2, as well as evaluating the effects of metformin treatment in metastatic capacity, and induce angiogenesis. These pathways are associated in different types of cancer, thereby the study of interference on their processes could be further used for other cancers beyond the biological model adopted. (AU)