Expressions Of Fas And FasL In Renal Cell Carcinoma (RCC) Tissues And Their Role In Drug Resistance Of RCC

Renal cell carcinoma (RCC) is one of the most common seen tumors in urinary system and the mechanism of RCC remains unclear with unsatisfactory therapeutic results. The general conservative treatment including radiotherapy, chemiotherapy and immunotherapy has unsatisfactory curative effect. The literatures have shown that there is no break-through in the treatment of RCC within two decades. With devolopment of biology, It is primarily considered that cellular canceration is due not only to increase of cell proliferation, but also to decrease of cell apoptosis that may help the development of the tumors. As an important part of cell apoptosis signaling transmission, Fas and FasL play a pivotal role in cell canceration and corresponding treatment. Chemiotherapy is one of the important comprehensive treatments because the tolerance of the malignant tumor is the main cause for failed treatment. Multidrug resistance (MDR) exists at large during the chemiotherapy for carcinoma, therefore, a good deal of studies have been carried out deeply on MDR both in China and abroad. In clinical, RCC is one of those tumors that have unsatisfactory therapeutic effect and can easily produce drug resistance (mostly natural drug resistance) with little susceptibility. There is lack of perfect therapies to improve the curative effect of RCC. Therefore, the study focus has been averted to drug resistance mechanism of RCC during the course of chemiotherapy for RCC. It has been proved that the main but not the only causes for the drug resistance of RCC are the overexpression of P-glycoprotein (P-gp) and the activity increase of Glutathione (GSH)-dependent detoxication enzyme system. The tolerance of tumor cells to apoptosis is a novel mechanism of MDR. Induction of tumor cell apoptosis may be that different chemiotherapy drugs reach the same goal by different routes. Among studies on cell apoptosis and carcinoma drugs, the effects of Fas/FasL pathway in drug resistance of tumor chemiotherapy is the most conspicuous one and play an important role in inducing the necrosis of drug-sensitive leukemia cell line, hepatocarcinoma cell line and melanoma. There is no report on the relation between Fas/FasL pathway and drug resistance of RCC cells yet. In our study we have observed the expressions of Fas and FasL and in the RCC tissues by means of immunohistochemical method so as to explore their expressioncharacteristics in the RCC tissues. Through immunocytochemical method, Western blot, RT-PCR, TUNEL and electron microscope, we have further observed the effect of chemiotherapy drug 5-fluorouracil (5-FU) in regulating the expressions of RCC cell line 786-0 Fas and FasL and the effects of 5-FU, anti-Fas monoclonal antibody, CH11 and neutralizing anti-FasL monoclonal antibody NOK-2 on the apoptosis and proliferation activity of RCC cell line 786-0. The effect of Fas/FasL pathway in drug resistance of RCC cells has been also studied aiming to provide a fresh strategy for solving the drug resistance of RCC cells. The main results are as follows:1. The positive expression of Fas in RCC tissues was significantly lower than that in normal renal tissues, but the positive expression of FasL in RCC tissues was significantly higher than that in normal renal tissues. There was a correlation between Fas expression and FasL expression in the normal renal tissues,but not in the RCC tissues.2. The protein expression rate of Fas and FasL showed no significant difference between pathological type and clinical stage. Fas protein expression rate decreased but FasL protein expression rate increased with increase of RCC cell grade with a significant difference between pathological grades of RCC. FasL protein expression was significantly higher in group with lymph node metastasis than that without lymph node metastasis. There was no significant difference in Fas protein expression between two groups. 3. The protein products of Fas and FasL expressed in human RCC cell line 786-0,mainly in cellular plasma and membrane rather than in cellular core.