The Research About Apoptotic Mechanisms Of Mitomycin And Epirubicin Against Bladder Cancer Cells And Intravesical Them Instillation For Preventing Tumor Recurrence

Objective:1.To investigate the apoptotic action mechanisms of mitomycin(MMC) and epirubicin (EPI) against human bladder cancer cells T24.2.To observe the clinical effects on intravesical different dosages and times of MMC and EPI instillation for preventing the recurrence of superficial bladder cancer after surgery with the purpose of providing more scientific theory basis for developing programs about reasonable intravesical therapy.Methods:1.Three different experimental technique,MTT assay,flow cytometry,light microscope and transmission electron microscope,were used to assess the effects of different concentrations of MMC and EPI on human bladder cancer T24cell line and the apoptotic action mechanisms.2.Patients of clinical multicentres were randomized into different groups and then were performed by a prospective controlled clinical trial.Patients were followed for the conditions about the disease free intervals, recurrence rate of tumor and side effects after surgery.Results:1.Basic research Both MMC and EPI can inhibit the growth of T24cells,and the depressive effects reinforcement along with increasing drug concentrations. When the concentrations of MMC and EPI were100mg/L, T24cells were suppressed greatly and the suppressive rates were90.1%and95.6%respectively. They can effect the cell cycle of T24cells,but the effects show no obvious rules.The characteristics of cells apoptosis were typically manifested, including the bubble formation in cytoplasm,cell shrinkage and cytoplasmic density,solution and fragmentation of the nucelus, crescent sample lesions and apoptotic body.those apoptosis peak which were evident before the G1phase.2.Clinical research The disease free intervals of group A-single80mg dose of MMC、B-20mg MMC consecutively、 C-single80mg dose of EPI、D-20mg EPI consecutively at1year after operation were found to have no differences (F, P>0.05).The recurrence rates were21.7%、16.0%、18.8%、23.8%,respectively(X2, P>0.05).The side effects rates were17.4%、44.0%、12.5%、42.9%,respectively(X2, P<0.05)Conclutions:1.Both of MMC and EPI can inhibit the growth and induce the apoptosis of human bladder cancer T24cells,which depends on drug concentration and might be one of the antitumor mechanisms of MMC and EPI.2.Both immediate intravesical large dose of MMC and EPI instillation and maintain intravesical routine dose instillation of superficial bladder cancer after operation can efficiently prevent the recurrence in the short term.Immediate instillation is more cheaper, convenient and less of side effects than maitain instillation, although the long-term effect of single intravesical MMC and EPI instillation remains to be studied.