Skip to main content
. 2019 Dec 23;13(2):275–286. doi: 10.1016/j.tranon.2019.10.003

Figure 1.

Figure 1

Antitumoral effect of BRAFi/MEKi in BRAF-mutated SKMEL28 xenografts treated with continuous/intermittent dosing schedules. (A): Ex vivo SKMEL28 HDRA. Percentage of cellular proliferation inhibition with continuous and intermittent dosing schedules during treatment with dabrafenib at 10 μM (BRAFi), cobimetinib at 1 μM (MEKi), or combination of both (BRAFi + MEKi) compared with control in SKMEL28 xenograft-derived histocultures, as determined by MTS assay. The results are representative of 3 independent experiments conducted in quadruplicate. (Mean ± SEM; #, P < 0.05 for continuous versus intermittent treatments; *P < 0.05, **P < 0.01, ***P < 0.0001 for continuous or intermittent treatment versus corresponding control; ns, non significant.) (B): In vivo SKMEL28 xenograft growth in nude mice treated with dabrafenib (100 mg/kg po once daily) or (C): with cobimetinib (5 mg/kg po once daily) with continuous and intermittent monotherapy dosing schedules compared with vehicle. (Mean ± SEM; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, non significant). Controls were treated with PBS-DMSO 5%. Five mice were tested in each treatment and control group. (D): Transcript levels analysis for BRAF or MEK inhibitor monotherapies. mRNA analysis performed on CTRL and continuous or intermittent dabrafenib or (E): cobimetinib-treated tumors by qRT-PCR on 30 genes involved in MAPK, cell cycle, or apoptosis pathways compared with the reference gene PPIA.(Mean ± SEM; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, non significant). The results are representative of 3 independent experiments conducted in triplicate.