Chemotherapy Desensitization of Liver Cancer Cells with ATGL Overexpression

Abstract

Adipose triglyceride lipase (ATGL) is a key enzyme in releasing fatty acids from triglycerides during lipolysis. ATGL can promote or inhibit cancer cell growth depending on the tissue. This experiment is testing the sensitization of chemotherapeutic agents in conjunction with ATGL overexpression in liver cancer. Three hepatocellular carcinoma cell lines (Hep3B, HepG2, and HUH7) were transduced and puromycin selected with two lentiviruses: one containing pLJM1 as a vector control and one containing hATGL to induce ATGL overexpression. Bodipy staining after oleate supplementation showed lower lipid droplet accumulation with ATGL overexpression for all cell types tested. Cell viability in standard and oleate supplemented conditions showed ATGL overexpression generally decreasing sensitivity to the FDA approved chemotherapeutic agent doxorubicin. The findings support the idea that the breakdown of triglycerides could be supporting the growth and viability of cancer cells. Future research on the mechanisms behind ATGL mediated drug resistance in relation to cancer therapy and oxidative stress could provide new targets for liver cancer treatments.