| Background: Multi-drug-resistance is the main cause of tumor chemotherapy failure with complicated mechanisms including increased drug efflux, intracellular drug redistribution, apoptosis transduction pathway and intra- and extra-cellular environment changement etc. Multi-drug resistance involves many drug resistance -related molecules, such as P-gp, MRP, GST, LRP, and TOPO II. It is important to explore the multidrug resistance mechanism and develop reversing methods. The clinical use of commonly reversing agents such as verapamil and cyclosporine A has been limited due to their toxicities and side effects. Tumor hyperthermia has been found to increase the sensitization of tumors to chemotherapy and radiotherapy and its underlying mechanism needs to be further studied. Objectives: To preliminarily study the reversing effect of temperature of 43°C on the drug-resistant human gastric cancer cell line SGC7901/ADM at molecular level and to observe the influence of this temperature on the development of drug resistance with chemical agents such as ADM, CDDP, 5-FU, and TAX. Methods and materials: Drug-resistant human gastric cancer cell line SGC7901/ADM and sensitive human gastric cancer cell line SGC7901 has been selected. Experimental methods including MTT test, RT-PCR, Western-blot methods, immuno-cyto-histochemical staining, Rho123 efflux trial, PI staining flow cytometry technology, and TUNEL, were employed to detect the effect of different temperatures and different drugs on the in-vitro drug sensitivity of SGC7901/ADM cell line and controlled SGC7901 cell line, and expression of multi-drug-resistance related MDR1, P-gp, MRP, LRP at level of mRNA andprotein, and the drug efflux of P-gp and influence on tumor cell cycles and cellular apoptosis.Results: It was found that drug resistant human gastric cancer cell line SGC7901/ADM showed not only resistance to the inductive ADM but also cross resistance to CDDP, 5-FU and TAX, and high-temperature of 43 °C could lower the survival rate of SGC7901/ADM and increased cell survival rate when being effected with chemical agents such as ADM, CDDP, 5-FU and TAX. MDRl, PGP, MRP, LRP were not detected in sensitive human gastric cancer cell line SGC7901. MDRl, PGP, MRP but not LRP were detected in drug resistant SGC7901/ADM cell line and high temperature of 43 °C could lower the expression of MDRl and P-gp and efflux of Rhol23. High temperature of 43 °C can increase the cell apoptosis when drug resistant SGC7901/ADM cell line were effected by ADM, CDDP, 5-FU and TAX.Conclusions: 1. high temperature of 43 °C could improve the sensitivity of drug-resistant SGC7901/ADM to chemical agents like ADM, CDDP, 5-FU and TAX;2. No drug resistant molecules were detected in sensitive SGC7901 cell line, MDRl and P-gp were the main factors related with drug resistance in SGC7901/ADM cell line, MRP can be detected in low level and LRP cant be detected. 3. high temperature of 43 °C could reduce the multi-drug resistance of SGC7901/ADM through MDRl pathway but not MRP or LRP. 4. High temperature of 43 °C could reduce the drug efflux effect of P-gp effected by ADM, CDDP and TAX. 5. high temperature of 43 °C promote cell apoptosis when drug resistant SGC7901/ADM cell line was effected by ADM, CDDP, 5-FU and TAX.
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