Journal: BMC Cancer
Article Title: Preclinical efficacy of dual mTORC1/2 inhibitor AZD8055 in renal cell carcinoma harboring a TFE3 gene fusion
doi: 10.1186/s12885-019-6096-0
Figure Lengend Snippet: Cell viability, cytotoxicity and cell cycle progression in TfRCC cell lines treated with mTOR inhibitors. a , b Cell viability, as measured by MTT assay for TfRCC cell lines and the benign renal epithelial cell line HRCE after 72 h of treatment with up to 1000 nM concentrations of the dual mTORC1/2 inhibitor, AZD8055 ( a ), or selective mTORC1 inhibitor, sirolimus ( b ). Viability in TfRCC cells was suppressed by approximately 80–90% with AZD8055 and 30–50% with sirolimus relative to the untreated (0 nM drug) condition. Both drugs inhibited growth to a greater degree in TfRCC cells than in benign renal cells. c , d Cell cytotoxicity, as measured by LDH release by UOK120 and UOK146 TfRCC cell lines after 48 h of treatment with 1 μM of AZD8055 ( c ) or sirolimus ( d ). Only slight cytotoxicity in UOK120 cells and no cytotoxicity in UOK146 cells was observed after AZD8055 treatment, while sirolimus treatment had no cytotoxic effect. Multi protein inhibitor LY294002 [100 μM] was used as a positive control. e , f Relative fraction of cells in S-phase of the cell cycle, as measured by BrdU incorporation in UOK120 ( e ) and UOK146 ( f ) cell lines treated for 24 h with low (50 nM) and high (500 nM) concentrations of AZD8055 or sirolimus. Dose-dependent reductions in S-phase in both cell lines with either drug mirror the magnitude of reductions observed in cell viability ( a , b ), supporting a predominantly cytostatic mechanism of growth inhibition for both drugs. * p < 0.05; ** p < 0.01; *** p < 0.001; NS = non-significant
Article Snippet: RCC4 was obtained from ECACC General Cell Collection (Salisbury, UK; Cat Nr. 03112702) and the human renal cortical epithelial (HRCE) cell line was obtained from ATCC (Manassas, VA; Cat Nr. PCS-400-011).
Techniques: MTT Assay, Positive Control, BrdU Incorporation Assay, Inhibition