Study On The Mechanism Of Multidrug Resistance In Squamons Cell Carcinoma Of Tongue And Effect Of Thermoradiotherapy On Its Expression

The multidrug resistance (MDR) to cytotoxic chemotherapy is a common problem in patients with cancer and a major obstacle to effective treatment. The MDR is characterized by tumor resistance to various drugs with different structure and function. Resistance can be intrinsic or acquired. Tumors with intrinsic resistance fail to respond to the first chemotherapy given. In acquired resistance, tumors initially respond to chemotherapy but eventually progress in spite of treatment.Various molecular mechanisms have been associated with MDR, Which include enhanced efflux of drugs by transporter proteins such as P-gp or MRP, alterations in drug targets such as DNA Topo â…¡. Increased detoxification of compoands by GST, and overexpression of LRP, which might play a role in vasicular sequestration of drugs.Besides surgery and radiothery, hyperthermia and chemotherapy have played a more and more important roles in the treatment of head and neck malignant tumors. The incidence rate of tangue squamous cell cancer is the highest of head and neck malignant tumors, but the knowledge about relationship of its MDR and thermoradiotherapy was limited. The aim(purpose) of this research is to study the relation between the effect of chemotherapy and the expressions of P-gp, MRP₁ and GST- Ï€ in patients and cell lines of cancer of tongue, trying to investigate the mechanisms of MDR in squamous cellcarcinoma of tongue and effect of the thermoradiotherapy on its expression.In this study, the expressions of P-gp, MRPi, GST- n , LRP and Topo II were investigated before exposure to chemotherapeutic reagents, in order to establish the relation of clinical stage, chemotherapy effect with expressions of MDR relative factors. Multidrug resistance cell line Tea 8113/CBDEA was established. In the Tea 8113, Tea 8113/CBDEA. Hgperthermia, radiotherapy or thermoradiotherapy were applied to them to observe the change of expression levels of MDR relative factors and intracellular concentration of drug.The results show that:1. Coexpression of P-gp, MRPi and GST- n casuse the insensitivity of tongue squamous carcinoma to chemotherapy.2. A multidrug resistance cell line (Tea 8113/CBDEA) was successfully established which has the basic characteristics of drug resistance cells.In which,the expressions of P-gp, MRPi and GST- n were increased remarkably.3. Hyperthermia increased intracellular drug concentration and suppressed the mRNA and protein expression of P-gp, MRPi and GST- n . Decreased tendency of P-gp, MRPi and GST- n in Tea 8113/CBDEA was significantly stronger than Tea 8113.4. Radiotherapy decreased intracellular drug concentration and induced the mRNA and protein overexpression of P-gp, MRPi and GST- n.5. Thermoradiotherapy restrain the overexpression of MDR relative factors induced by radiotherapy, slightly suppressed the MRPi and GST- n expression and increased intracellular drug concentration.