Figure 7.

 Effects of insulin-like growth factor I receptor (IGF-Ir) on in vivo tumorigenicity and tumour growth. (A) MKN45 cells infected with adenoviruses expressing truncated IGF-Ir of 482 amino acids long (Ad-IGF-Ir/482st) or adenovirus expressing β-galactosidase (Ad-LacZ) were inoculated subcutaneously into nude mice (n = 6 per group). Although cells infected with Ad-LacZ formed subcutaneously tumours, mean (SEM) size was 870 (347) mm³; after 49 days, cells expressing IGF-Ir/482st did not form any tumours. (B) Established palpable subcutaneously MKN45 tumours (mean (SEM) size 153 (13) mm³) were directly injected with 1×10⁸ PFU of adenoviruses on five successive days and tumour volumes measured (n = 12/group). Both Ad-IGF-Ir/dns significantly reduced tumour growth; tumour volume with Ad-LacZ was 1001 (202) mm³, 506 (29) mm³ with adenoviruses expressing truncated IGF-Ir of 950 amino acids long (Ad-IGF-Ir/950st), and 377 (55) mm³ with Ad-IGF-Ir/482st, 21 days after treatment (**IGF-Ir/482st v control, p = 0.0041; †IGF-Ir/950st v control, p = 0.0257). (C) Combination therapy of 5-fluorouracil (5-FU 50 mg/kg) and IGF-Ir/482st was assessed. After forming subcutaneously MKN45 tumours, 1×10⁸ PFU of Ad-IGF-Ir/482st or Ad-LacZ were injected intratumorally (it) on five successive days and 5-FU or vehicle (phosphate buffered saline (PBS)) was injected (intraperitoneally (ip)) four times, once a week (n = 12/group). Both 5-FU alone and IGF-Ir/482st alone suppressed tumour growth (p = 0.0041 and 0.0018, respectively). The combined therapy was the most effective (p<0.0001 compared with control) and two tumours were cured.