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. 2022 Jun 29;29:969–978. doi: 10.1016/j.omtn.2022.06.001

Figure 4.

Figure 4

Anti-cancer effect of APT-β1-OMe-P in xenograft cancer model

(A) Experimental schedule of xenograft cancer study. Mice with PC3 and PC9 cancer xenografts were treated with APT-β1-OMe-P (10 mg/kg b.w./day) and/or gefitinib (100 mg/kg b.w./day) or their vehicle as a control during indicated periods (details in Materials and methods). (B) In vivo luminescent signals of xenografts in each treatment group are shown. Cancer xenografts expressing the fire luciferase gene in each treatment group were examined by an IVIS imaging system at indicated days. Until the first sampling day at day 24 or day 25, the in vivo imaging was carried out in 10 or 9 mice per group in PC3 or PC9 xenograft, respectively; after the day 24, the monitoring was continued in the remaining 5 or 4 mice per group. (C) Wet weight of tumors in each treatment group is shown. Tumors at day 24 and day 49 in each group in PC3 xenograft (left panel) and at day 25 and day 46 in each group in PC9 xenograft (right panel) were isolated (left panel), and their wet weight was examined (right panel). Statistical differences among treatment groups were examined by two-way ANOVA and then by Sidak multiple comparisons. Data represent the mean ± SD (n = 5 except for at day 46 in PC9; n = 9 at day 46 in PC9 xenograft). (D) Effect of APT-β1-OMe-P on xenografts in drug withdrawal and gefitinib re-treatment periods is shown. To widely evaluate anti-cancer effect of APT-β1-OMe-P on PC3 and PC9 xenografts, the effects of withdrawal period and re-treatment of gefitinib in each treatment group were examined by the ratio of luminescent signals between day 24 and 36 (day 36/day 24), between day 36 and 49 (day 49/day 36) in PC3 xenograft (left panel), between day 25 and day 39 (day 39/day 25), and between day 39 and day 46 (day 46/day 39) in PC9 xenograft (right panel), respectively. As in (C), statistical differences among treatment groups were examined by two-way ANOVA and then by Sidak multiple comparisons. Data represent the mean ± SD (n = 5 except for at day 46 in PC9; n = 9 at day 46 in PC9 xenograft).