CXCR4 blockage induces cytotoxic effects in liver cancer cells

Abstract

Background: Hepatocellular carcinoma (HCC) is a malignant tumor which arises from the liver cells (hepatocytes). Chronic inflammation followed by fibroses and cirrhosis ultimately leads to the development of liver carcinoma. Various treatment strategies for HCC include surgery, radiotherapy, targeted agents and chemotherapy. Despite the availability of diverse therapeutic options, 5-year survival rates are low (10-30%) especially in advanced stages of HCC. This, in turn, highlights the need to identify new therapeutic targets/compounds for HCC treatment. The purpose of this study was to evaluate the effects of blocking chemokine receptor (CXCR4) on cell proliferation and apoptosis related genes (FAS/FASL) in liver cancer cells (HepG2).

Methods: CXCR4 receptors were blocked by using FDA approved respective antagonist (AMD3100) in HepG2 cells and effects on proliferation were identified. For this purpose, the cells were exposed to various concentrations (7.5-500µM) of the test compound and cell viability was monitored by MTT dye reduction assay for 24, 48 and 72 hours. Afterwards, HepG2 cells were exposed to three distinct concentrations of AMD3100 (50, 100, 200µM) in a separate experiment and expressional modulations in two apoptosis related genes (FAS and FASL) were identified by qRT-PCR methodology.

Results: Blocking CXCR4 by using AMD3100 induced minimal growth inhibitory effects on the cells. Blockage of CXCR4 induced marginal up-regulation of FAS and FASL genes in the cells.

Conclusion: Further investigations are needed to discover the effects of CXCR4 blockage on liver cancer cells.