The investigation on the characteristics of colorectal cancer stem-like cells and therapeutic strategies

Recent studies have indicated that cancer stem-like cells (CSCs) exhibit a high resistance to current therapeutic strategies, including photodynamic therapy (PDT), leading to the recurrence and progression of colorectal cancer (CRC). Therefore, more effective anticancer strategies targeting CSCs will be critical for developing a cure for cancer. In this study, CSCs were isolated from colorectal cancer cells using CD133 expression and analyzed it’s stemness-associated properties. We demonstrated first that autophagy may be the main cause of resistance to PpIX-mediated PDT in CD133+ cells. The inhibition of PDT-induced autophagy by pharmacological inhibitors and silencing of autophagy-related gene substantially triggered apoptosis of CD133+ cells and decreased the ability of colonosphere formation in vitro and tumorigenicity in vivo. Second, we elevated ROS levels to improve the cytotoxicity of PDT to CSCs by inhibition of thioredoxin 1 (Trx1). In addition, we found that silencing of Trx1 reduced the ability of sphere formation of CD133+ cells and sensitized CD133+ cells to conventional chemotherapy. Third, we increased the percentage of CD133+ cells in cancer population and established an in vivo CSCs model by inducing EMT in colorectal cancer cells. Cells underwent an EMT are more efficient in tumor-initiating potential and increase stemness-associated properties. Based on the results, these findings would aid in the development of novel therapeutic approaches for CSC treatment.