Identifying Senescence as a Mode of Chemo Resistance in Ovarian Cancer

Abstract

Current treatments of ovarian and breast cancer result in chemo resistance all too often. It has been hypothesized that senescence-a dormant condition associated with increased age and apoptosismay play a role in the development of chemo resistance. We performed an in-vitro study with HOSE (carboplatin-sensitive), SKOV3 (chemo resistant ovarian cancer), and CAMA1 (chemo resistant breast cancer) cell lines, which were exposed to a variety of platinum-based treatments meant to model current cover clinically relevant scenarios in terms of tumor hypoxia. They were then stained for senescence in-vitro using B-gal, and analyzed for proliferation using the Cell Counting Kit 8, trypan blue dye exclusion, and survival plating, among other methods. Real-time quantitative PCR was used to determine relative levels of gene expression for classical apoptotic and senescent markers. Our results indicate that proliferation was temporarily halted in SKOV3 and CAMA1 after treatment. Cell proliferation later resumed in these cell lines while HOSE cell underwent apoptosis. Analysis of genetic tests (such as qPCR) also revealed that SKOV3 and CAMA1 had decreased gene expression of key genes that regulate apoptosis and senescence (such as p53 and CDK2). It can be concluded from this data that senescence was in fact a mode of chemoresistance and that future treatments may want to focus on disabling cancerous cells’ senescent stage.