Journal: Cells

Article Title: PIK3R1 W624R Is an Actionable Mutation in High Grade Serous Ovarian Carcinoma

doi: 10.3390/cells9020442

Figure Lengend Snippet: Response of PIK3R1 W624R carrying PDTCs to inhibitors of the PI3K/AKT/mTOR pathway. In each experiment, control cell lines were assayed, too. ( A , C , E , G ): Dose-response curves in CellTiterGlo 72 h viability assays. Normalized growth rate (GR value) inhibition metrics of three replicate experiments is shown to take into account cell division rates. The sign of GR values relates directly to response phenotype: positive for partial growth inhibition, zero for complete cytostatic effect and negative for cytotoxicity. The x axis shows drug concentration on a log 10 (Log) scale. ( B , D , F , H ): Western blot analysis of the phosphorylation of the AKT signal transducer in response to drugs, as a proxy of PI3K activation status. ( A ) The PIK3R1 W624R PDTCs showed susceptibility to the pan-class I PI3K inhibitor buparlisib (BKM120), comparable to that of the highly responsive A2780 cells; ( C ) the PIK3R1 W624R PDTCs showed susceptibility to the dual PI3K/mTOR inhibitor dactolisib (BEZ235), comparable to that of the most sensitive (OVCAR-8) of the above cell lines; ( E ) the PIK3R1 W624R PDTCs were also highly susceptible to the p110α specific PI3K inhibitor alpelisib (BYL719) as well as the A2780 cells; and ( G ) resistant to the p110β specific inhibitor GSK2636771 to which the LNCaP cells are exquisitely susceptible.

Article Snippet: The A2780 (NCI-DTP Cat# A2780) ovarian carcinoma cells lines and the LNCaP prostate carcinoma cell line (CLS Cat# 300265/p761_LNCaP) were purchased from American Type Culture Collection (ATCC,).

Techniques: Inhibition, Concentration Assay, Western Blot, Activation Assay