1. Fig. 6. Combinatorial VCPI and OV M1 treatment is efficacious in vivo and ex vivo.
Combinatorial VCPI and OV M1 treatment is efficacious in vivo and ex vivo. (A) Timeline of the experimental setup for (B) and (C). (B) Hep3B xenografts were treated with vehicle, M1 virus (5 × 105 PFUs, intravenously), EerI (2 mg/kg, intraperitoneally), or a combination. Data are mean tumor volume ± SD (eight mice per group). ***P < for M1-EerI combination versus single agents. (C) Huh 7 xenografts were treated with vehicle, M1 virus (5 × 105 PFUs, intravenously), EerI (2 mg/kg, intraperitoneally), or a combination. Data are mean tumor volume ± SD (eight mice per group). ***P < for M1-EerI combination versus single agents. (D) Timeline of the experimental setup for (E). (E) Kaplan-Meier survival curve of mice bearing Hep3B tumors treated with vehicle, M1 virus (1 × 106 PFUs, intravenously), EerI (2 mg/kg, intraperitoneally), or a combination. CTL, n = 7; EerI, n = 7; M1, n = 8; M1 + EerI, n = 8. ***P < 0.001, log-rank with Holm-Sidak multiple comparisons. (F) Representative images of livers from each group in (E) at day 15. Dashed blue lines represent tumor areas. (G) Timeline of experimental setup for (H). (H) Kaplan-Meier survival curves of immunocompetent mice bearing Hepa1-6 tumors treated with vehicle, M1 virus (1 × 106 PFUs, intravenously), CB-5083 (25 mg/kg, orally), or a combination. CTL, n = 6; CB-5083, n = 5; M1, n = 6; M1 + CB-5083, n = 6. ***P < 0.001, log-rank with Holm-Sidak multiple comparisons. (I) Representative images of livers from each group in (H) at day 15. Dashed blue lines represent tumor areas. (J) Tumor tissues from (F) were evaluated through immunohistochemistry for Ki-67 (a marker of proliferation), IRE1α (a marker of the UPR pathway), p-JNK (a marker of ER stress–induced apoptosis), cleaved caspase-3, and E1 (structural protein of M1 virus). N, nontumor area; T, tumor area. Scale bar, 50 μm. (K) HCC tissues from five patients were treated with vehicle, EerI (10 μM), M1 (2 × 106 PFUs), or a combination for 96 hours, and cell viability was assessed. (L) Amounts of VCP protein in five patients. P, patient. Quantification (indicated by the numbers at the top) was performed using ImageJ software. (M) Correlation of cytotoxicity and relative VCP expression. r is the Pearson correlation coefficient.
Haipeng Zhang et al., Sci Transl Med 2017;9:eaam7996
Published by AAAS