| Chemotherapy is one of the comprehensive treatments of the bladder carcinoma. At present it is generally acknowledged that MMC is the most commonly used in bladder transfusion chemotherapy and is one of the chemotherapeutic drugs that can get better effect. If traditional high dose ( 1. 000mg/ml) MMC is used in bladder transfusion chemotherapy, it often injuries normal tissues, reduces local immunity and causes some side effects such as bone marrow inhibition, chemical cystitis and stricture of the urethra when killing tumor cells. How to find a balancing point between curative effects and side effects is a big problem in bladder transfusion chemotherapy that not only can maximally kill tumor cells, but also decrease side effects to the minimum. In the past study we demonstrated that low dose MMC can induce bladder cancer cell apoptosis, its effect depends on triggering apoptotic mechanism. In this complicated mechanism, Fas/FasL which acts as death receptor - ligands and caspase - 3 as death proteinase may be important.Fas,N FasL and Caspase -3 are apoptosis -related genes. Fas ,is a type I transmembrane glycoprotein, apoptotic signaling receptor. FasL is a type II gly-coprotein, natural ligand of Fas, it establishes Fas/FasL apoptotic signaling transductional system with Fas. When FasL combines with Fas on cell surface in trimer, Fas/FasL can trigger apoptotosis related gene products, then conduct death signal to cells, lead to cellular apoptosis which expresses Fas. Caspase -3 is the most important member in caspase family. It plays a key role in death receptor mediated and/or chemotherapy induced cell apoptosis which is represented by Fas/FasL. Recent studies indicate that the factors causing apoptosis in vitro and in vivo, such as chemotherapeutic drugs,Fas and so on, need to activate caspase firstly, such as caspase -8 et al, then activate caspase -3, finally lead to cellular apoptosis. It's pointed out that Fas/FasL interaction is one important way, while caspase - 3 plays an important role in chemotherapy inducingapoptosis. The mechanism of chemotherapy inducing tumor cell apoptosis can be divided into three stages; first, occurrence of injury, second, conduction of injuring signal, and third susceptible cells present answering reaction and apoptosis to injuring signals.In this study, cell culture,cell proliferation kinetics, cell morphology , im-munohistochemistry,TUNEL staining,FCM and Western Blotting et al are applied. From occurrence of apoptosis,signaling conduction and modulation, we inquired the intrinsic mechanism, characteristics and clinical significance that low dose MMC induced bladder cancer cell apoptosis and inhibited proliferation. Our studies indicate:Low dose MMC induces bladder cancer cellular apoptosis in vitro1. To induce cell apoptosis is the main mechanism of low - dose MMC inib-iting the proliferation of EJ cells of bladder carcinoma: ( 1) injury of DNA; (2) transduction of injury signal; (3) sensitive cancer cells react to injury signal and result in apoptosis.2. Fas, FasL, Caspase -3, these apoptosis -related gene take part in the apoptosis and its control induced by low dosage MMC and (or) mediated by Fas system.In vitro Caspase - 3 action in low dose MMC inducing bladder cancer cell apoptosis3. It is proved that Caspase - 3 could resist EJ cellular apoptosis induced by low -dose MMC.4. Caspase - 3 played an important role in the induction of apoptosis by low -dose MMC.5. Our experiments provided a new target point for managing the ways of chemotherapy to carcinomaFas , FasL,Caspase -3 expression and significance in bladder cancer tissue treated by low dose MMC in vivo6. The low - dosage MMC (0. 5mg/ml) could induce the apoptosis of bladder cancer in Vivo.7. Fas, FasL and Caspase -3 play a role in the cell apoptosis of bladder cancer induced by low - dosage MMC.8. Fas and Caspase -3 was decreased with the bladder cancer grades and stages. FasL was increased with the grades and stages, which might be one of th...
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