Fig. 6

Cyst(e)inase synergistically inhibits growth of pancreatic cancer xenografts in combination with auranofin without toxicity. a Growth of xenografted BxPC3 pancreatic tumors in male nude mice treated with vehicle control (n = 8 mice), cyst(e)inase (Cys, n = 8 mice), auranofin (Aur, n = 8 mice), or cyst(e)inase and auranofin in combination (n = 7 mice), and waterfall plots indicating the percent difference from median tumor volume of vehicle-treated group at day 42. b Average body weight (top), liver toxicity as assessed by serum alanine aminotransferase (ALT) activity (middle), and renal function as assessed by serum urea concentration (bottom) in mice from a. c, d Representative immunohistochemical staining c of xenografts from a, and their quantification d, which was performed in ImageJ software. Scale bars, 500 μm (Inset: 100 μm). e Growth of xenografted MIA-PaCa2 pancreatic tumors in male nude mice treated with vehicle control (n = 8 mice), cyst(e)inase (n = 8 mice), auranofin (n = 9 mice), or cyst(e)inase and auranofin in combination (n = 9 mice). f Isobologram of the effect of the combination of cyst(e)inase (Cys) and auranofin on BxPC3 and MIA-PaCa2 xenografts. All data represent mean ± s.e.m. *P < 0.05, **P < 0.01, ****P < 0.0001; compared to vehicle controls; repeated-measures two-way ANOVA (a, e) or two-way ANOVA (b, d) with Bonferroni’s method for multiple-comparison test