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. 2018 Jun 26;8:9711. doi: 10.1038/s41598-018-28002-y

Figure 7.

Figure 7

PRMT5 inhibition leads to tumour growth attenuation in lymphoma xenograft models. (A) Tumour volume in a Z-138 mouse tumour xenograft with 21 days of GSK3326595 treatment. Groups undergoing treatments that resulted in statistically significant decreases in tumour volume (i.e. 50 mg/kg BID, 100 mg/kg BID and 200 mg/kg QD) were placed on a treatment holiday for 10 days to assess the durability of the response. Treatment was re-instated on day 32 for 2 weeks followed by a 1 week holiday. The 25 mg/kg BID dose group was euthanized on day 35 due to tumour burden. BID doses evaluated include 0, 0.2, 0.5, 1.4, 4.2, 12.5, 25, 50, and 100 mg/kg. QD doses evaluated include 0, 50, 100, and 200 mg/kg. A statistically significant dose-dependent anti-tumour effect was observed for the 25 mg/kg BID, 50 mg/kg BID, 100 mg/kg BID, and 200 mg/kg QD treatment groups (corresponding percent tumor growth inhibition values, % TGI, of 52.1%, 88.03%, 106.05%, and 102.81%, respectively). (B) SDMA in Z-138 tumour xenograft model post 7 days treatment with GSK3326595 with twice daily oral dosing. Sampling 2 hours post last dose. Tumour growth inhibition is indicated from a parallel efficacy study. SDMA % vehicle: 94%, 71%, 47%, 28%, 9%, 5%, 8%, 2% in mice given 0.2 mg/kg, 0.5 mg/kg, 1.4 mg/kg, 4.2 mg/kg, 12.5 mg/kg, 25 mg/kg, 50 mg/kg, or 100 mg/kg GSK3326595 BID and SDMA % vehicle: 16%, 12%, and 9% in mice given 50 mg/kg, 100 mg/kg, 200 mg/kg GSK3326595 QD. (C) Effects of 100 mg/kg BID GSK3326595 treatment for 7 days on p53 protein levels in Z-138 tumours by immunohistochemistry. (D) Tumour volume in a REC-1 (p53 mutant) mouse tumour xenograft treated with 100 mg/kg BID GSK3326595 or vehicle.