The tumour cellular senescence index: quantifying the effect of doxorubicin in inducing senescence in human A2780 ovarian cancer cells

Abstract

Therapy induced senescence (TIS) refers to senescence caused in cancer cells by anti-cancer agents. Many investigations indicate that TIS may increase invasiveness, survivability, and stemness in tumour cells. The goal of this study was to quantify changes in the expression of senescence-related genes (SRGs) in doxorubicin (DOX)-treated human A2780 cells to compute a tumour Cellular Senescence Index (CSI). Additionally, we examined the relationship between the CSI in DOX-selected cells and their sensitivity to DOX. Reverse transcription quantitative PCR (RT-qPCR) studies revealed that 6 SRGs (PAI1, CDKN1A, MKI67, ANKRD1, MMP1, and MMP3) reproducibly changed expression relative to 3 reference genes (GAPDH, RER1, and RPS28) as cells acquired DOX-induced senescence. Computed CSI values substantially increased as the exposure time to DOX increased. Higher tumour CSI values in DOX-induced senescent cells were found to be associated with increased DOX sensitivity, as seen through increased DOX-induced ribosomal RNA degradation (RNA disruption).