Collagen Type I Induces a Balance in the Expression of Anti- and Pro-Apoptotic Genes in Hepatocellular Carcinoma Cells

Background: The importance of extracellular matrix (ECM) components in the progression of hepatocellular carcinoma (HCC) has been shown in many studies. Although restoring or activating apoptosis in tumors is an active area of cancer research, little is known regarding the effects of collagen type I, the main ECM component in the liver, on apoptosis of HCC cells. Here, we investigated the apoptotic profiles of HCC cells in a microenvironment with collagen type I. Method: In this in vitro study, we assessed the effects of collagen type I on HepG2 cells in pre-confluent and confluent states. We determined the mRNA levels of 25 genes, which are the key players of apoptosis. Flow cytometry-based apoptosis detection was performed by use of Annexin V/PI staining. Confocal laser scanning microscopy was used to assess P53 immunofluorescence in the cells. Results: The microenvironment with collagen type I and the confluency state of HepG2 cells affected the expression of 13 genes involved in apoptosis. We observed no significant change in the number of cells undergoing apoptosis depending on the confluency state or the presence of collagen type I. P53 immunofluorescence demonstrated no significant changes. Conclusion: We propose an apoptotic balance concerning overall cell survival, which might be caused by the counteraction of positive and negative mediators of apoptosis. This study might provide data for the involvement of collagen type I in apoptotic responses of HCC and contribute to a better understanding of cancer microen-