Background
Doctors have always been overwhelmed by tumor drug resistance because it is a major challenge in the clinical treatment of tumors. Cellular senescence has a strong relationship with the development of tumor drug resistance. Herein, we aimed to explore new regulatory factors involved in the aging process of colorectal cancer (CRC) cells and assess the effect of cellular senescence on CRC drug resistance.
Conclusions
Our results suggest that E2F1 suppresses the aging of CRC cells and tumor cells develop resistance to oxaliplatin through high E2F1 expression. Moreover, E2F1 may act as a possible target for oxaliplatin resistance studies.
Methods
Genes associated with cellular senescence for anticipating regulatory factors were first used, and the regulatory molecules of survival significance were then identified based on the
Results
On combining the database analysis results with those of our studies, we found that E2F1 was a critical regulator of cellular senescence in CRC. In the in vitro experiments, the E2F1 overexpression significantly stimulated the proliferation, invasion, and migration of CRC cells and even reduced oxaliplatin-induced senescence, further enhancing their resistance to oxaliplatin. Conversely, the tumorigenesis of colorectal cancer was repressed after the suppression of E2F1. Furthermore, CRC cells, which were otherwise resistant to oxaliplatin, also showed senescent phenotypes. Conclusions: Our results suggest that E2F1 suppresses the aging of CRC cells and tumor cells develop resistance to oxaliplatin through high E2F1 expression. Moreover, E2F1 may act as a possible target for oxaliplatin resistance studies.