Turkish Journal Of Biology, cilt.43, ss.24, 2019 (SCI Expanded İndekslerine Giren Dergi)
The second leading cause of cancer-related death worldwide is hepatocellular carcinoma (HCC). Currently, there is no specific drug for anti-metastasis treatment in HCC. Drugs used both for the treatment of primary HCC tumors and even for fighting with tumor metastasis are very similar. The cytotoxic drugs used are cisplatin, doxorubicin and 5-FU. Epidermal growth factor is an important mitogen for hepatocytes. Hepatocellular carcinogenesis is promoted by its overexpression. Moreover the EGFR pathway plays an important role in promoting hepatocellular carcinoma (HCC) metastasis although the mechanism remains unclear. Acetylcholinesterase and acetylcholin receptors which comprise the cholinergic system have been detected in HCC. Furthermore ACh promotes HCC cell proliferation, which correlates with the tumor aggressiveness, and low survival rate. However, the function and molecular mechanism of cholinergic system in hepatic carcinogenesis remain unknown. Different researcher suggested that long chain saturated fatty acids induce apoptosis and reduce cell viability in liver cells. They showed that exposure of human HepG2 hepatoma cells to palmitate result in apoptosis.
The aim of the present study was to investigate the role of EGFR-AChR signalling pathway in the human hepatocellular carcinoma (HCC) regarding proliferation and apoptosis. Using the hepatoma cells as a model system, we analyzed the combined effects of EGFR, cholinergic receptors and 5-FU on cell proliferation and effects of the apoptotic pathway including BCL/BAX and caspase-3. We suggest that activation of M3R and EGFR pathway might be a potential mechanism for ACh induced cell growth. Additionaly M3AChR antagonism of 4-DAMP combined with 5-Fluorouracil (5-Fu) might effect the cell viability and apoptosis in HepG2 cells and steatotic HepG2 cells.