Fig. 5: MEK1/2 inhibition significantly increases survival and reduces tumor growth in MB xenograft models. | Cell Death Discovery

Fig. 5: MEK1/2 inhibition significantly increases survival and reduces tumor growth in MB xenograft models.

From: Cross-species analysis of SHH medulloblastoma models reveals significant inhibitory effects of trametinib on tumor progression

Fig. 5

A Schematic outlining the 3 xenograft mouse model experiments. 2.5 × 105 cells/animal (UI226), 3 × 105 cells/animal (RCMB18) or 5 × 104 cells/animal (HDMB03) were injected into the cerebellum of immunodeficient NOD/SCID or NSG mice. Trametinib was administered via oral gavage on a 5 day on, 2 day off schedule following tumor engraftment. Treatment started 6 days after tumor engraftment for the HDMB03 cells and 14 days after tumor engraftment for the UI226 and RCMB18 cells. B, C Representative images of immunohistochemical staining for anti-mitochondria antibody (B) and p-ERK antibody (C) in FFPE tissue sections derived from 3 representative independent control tumors from UI226 SHH MB, RCMB18 SHH MB and HDMB03 Group 3 MB xenografts. Scale bar: 1550 μm. D–F NOD SCID and NSG mouse weights over time following vehicle control (black) or 1.5 mg/kg trametinib treatment (blue) post tumor engraftment with UI226 SHH MB cells (N = 10 mice for each treatment group) (D), RCMB18 SHH MB cells (N = 5 mice for each treatment group) (E) or HDMB03 Group 3 MB cells (N = 6 mice for each treatment group) (F). Drug treatment was initiated at day 14 following injection of UI226 and RCMB18 tumor cells and at day 6 following injection of HDMB03 tumor cells. Error bars: SEM. G Representative MRI images of UI226 SHH MB tumors in NOD SCID mice treated with vehicle control or 1.5 mg/kg trametinib at day 66 post-surgery. H–J Kaplan Meier curves following transplantation of NOD SCID mice with 2.5 × 105 UI226 SHH MB cells (N = 10 mice for each treatment group) (H), NSG mice with 3.0 × 105 RCMB18 SHH MB cells (N = 5 mice for each treatment group) (I), and NOD SCID mice with 5.0 × 104 HDMB03 Group 3 MB cells (N = 6 for each treatment group) (J). Mice were treated with vehicle control or 1.5 mg/kg of trametinib. P value was determined using the log-rank test. **, p < 0.01. For UI226 in (H): p = 0.0077. For HDMB03 in (J): p = 0.0012. Treatment started 14 days following UI226 and RCMB18 tumor cell injection and 6 days following HDMB03 tumor cell injection. Animals were treated once daily, 5 days a week by oral gavage, with a 2 day drug holiday on weekends until they reached endpoint.

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