Epigenetic modifications affect the radiosensitivity of three dimensional cultured carcinoma cells

B. Hu, D. Pan, G. Xue, Y. Chen, Y. Du
Institute of Modern Physics, Chinese Academy of Sciences,

Keywords: epigenetic modification, radiosensitivity, three dimensional cultured cell, matrigel


Three dimensional (3D) culture in vitro is a new cell culture model that more closely mimics the physiology features of the in vivo environment and is being used widely in the field of medical and biological research. It has been demonstrated that cancer cells cultured in 3D matrices are more radioresistant compared with cells in monolayer (2D). However, the mechanisms causing this difference remain largely unclear. Here we found that the cell cycle distribution and expression of some cell cycle regulation genes in 3D A549 cells were different from the 2D. The methylation in the promotor of some cell cycle regulation genes were observed in 3D A549 cells compared with cells in 2D. Whether do these differences result in the higher cellular radioresistance in 3D than 2D cells? We found that knockdown of the expression of RBL1 enhanced the radioresistance of 2D cultured cancer cells and overexpression of RBL1 in 3D cells enhanced the radiosensitivity. In addition, we found that cancer cells cultured in a 3D microenvironment demostrated an increase in cells with stem cell properties, such as the upregulated OCT4, SOX2, NANOG, LIN28 and miR-302a, compared with cells in monolayers. It was reported that cancer stem cell–like cells demonstrate an increased radio-resistance and chemo-resistance. Our findings shed new light on understanding the features of the 3D cultured cell model and its application in basic research into clinical radiotherapy and medcine development.