Occurrence of senescence-escaping cells in doxorubicin-induced senescence is enhanced by PD0332991 a cyclin-dependent kinase 4/6 inhibitor in colon cancer HCT116 cells

摘要

Cancer treatment induces cellular senescence, and it is considered to be one of the factors that determines treatment outcome. Senescence can be efficiently induced in cultured cells by DNA-damaging drugs, including doxorubicin (DOX), cisplatin and etoposide. Cells in senescence cease proliferation; however, it has been demonstrated that colonies that are formed from cells escaping senescence appear in drug-induced senescence; however, the conditions influencing the emergence of such senescence-escaping cells (SECs) remain unclear. The present study aimed to investigate the relevance of the cell cycle phase and colony formation in the DOX-induced senescence of human colon cancer HCT116 cells. After release from serum starvation in the presence of DOX, cells synchronously progressed through the cell cycle and were arrested in the G1 and G2/M phases. The ratio of G1 cells arrested immediately by the treatment of G1 phase cells was positively associated with the number of colony-forming cells. A procedure increasing G1-treated G1-arrested cells enhanced colony formation. Co-treatment of PD0332991 with DOX slowed progression of cells in the G1 phase resulting in enhanced colony formation from the increased G1-treated G1-arrested cells. These results may provide useful insights into understanding the emergence of SECs in drug-induced senescence.