Synergistic Anti-proliferative Effects of Lenalidomide and Dexamethasone on the HT-29 Cell Line Through Apoptotic Genes

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer among men and the second most common type of cancer among women worldwide. The resistance of tumor cells to apoptosis is caused by changes in the expression of anti-apoptotic or pro-apoptotic proteins. Histone deacetylase inhibitors (HDACi) are known to cause changes in gene expression. Objectives: The present study aimed at investigating the anti-proliferative effects of lenalidomide (LEN) as HDACi and dexamethasone (DEX) on the human colon cancer HT-29 cell line. Methods: The HT-29 cell line was treated with various concentrations of LEN and DEX individually and in combination for 24, 48, and 72 hours. Cytotoxicity was evaluated by MTT assay. The half-maximal inhibitory concentration (IC50) was measured, and quantitative real-time polymerase chain reaction (qRT-PCR) was also performed to examine the expression of Bcl2, Bax, Fas, and FasL genes. Results: The combination of LEN (1000 µM) with DEX (100 µM) showed potent synergistic anti-proliferative activities in a time- and dose-dependent manner. The combination of these drugs induced cell death by affecting the extrinsic and intrinsic apoptotic gene expression profiles. Conclusions: The combination of LEN with DEX can be proposed as a new therapeutic approach for CRC.