Induction of apoptosis by mitomycin-C in an ex vivo model of bladder cancer

Objective To examine mitomycin-C (MMC)-induced apoptosis in an ex vivo mode l of superficial TCC, and relate it to the in vivo response to chemotherapy . Materials and methods Dose- and time-response curves were constructed to de termine the optimal conditions for the induction of apoptosis by MMC in an ex vivo model of superficial bladder cancer. Subsequently, 41 individual tu mours were exposed to MMC in the model and the effects assessed by measurin g of apoptosis before and after chemotherapy. The relationships between tum our grade and stage and the intrinsic and induced apoptotic counts were det ermined. In tandem, in a clinical study, the relationship between in vivo r esponse of a marker tumour to MMC and the ex vivo induction of apoptosis wa s determined. Results In the ex vivo model, apoptosis was induced at a MMC concentration of 0.5 mg/mL after an incubation time of 8 h. In 41 tumours the intrinsic a poptotic index (AI) was higher with increased grade and stage of tumour (P = 0.048). There was no correlation between the intrinsic AI and the AI afte r treatment with MMC (induced AI). In 21 tumours (51%) the induced AI did n ot increase above a predetermined response threshold and these tumours were considered resistant to MMC. Resistance to MMC was related to tumour grade (P = 0.037) with a trend for G3 pT1 tumours to be resistant to the therapy . There was a significant association between ex vivo sensitivity and in vi vo marker tumour response (P = 0.02). Conclusions Apoptosis is differentially induced in an ex vivo incubation mo del of superficial TCC by MMC and evidence suggests that this response matc hes that seen in vivo. The measurement of apoptosis before therapy does not predict the apoptotic response of a tumour to chemotherapy. The ability to undergo apoptosis correlates with clinical outcome.