Study Of The Reversal Effect Of Heating Combined With Br-Tet On Multidrug-resistant Breast Cancer Cell Line MCF-7/ADM

[Objectives] Multidrug resistance (MDR) is the most common cause of chemotherapy failure. It is well established that the majority of tumors develop MDR through over-expression of the drug efflux pump P-glycoprotein (P-gp). Thermochemotherapy have been proved could increase sensitivity of multidurg-resistant cells to chemotherapeutic drugs .Br-Tet is a novel multidrug-resistant reversal agent, which is from a Chinese herb named tetrandrine. Experiment in vitro and vivo indicated that chemotherapeutic drugs such as ADM combined with Br-Tet could increase the sensitivity of multidrug-resistant cells to ADM by inhibiting the drug efflux pump P-gp. The purpose of this study was investigate the reversal effect of Br-Tet combined with heating and ADM on multidrug-resistant breast cancer cell line MCF-7/ADM[Methods] At different temperature 37℃, 40℃, 41℃, 42 ℃ /The multidurg resistant ,breast cancer cell line MCF-7/ADM was treated with lug/ml ADM; 0.125umol/l+lug/mlADM;0.25umol/lBr-Tet+lug/mlADM;0.5umol/lBr-Tet+ lug/mlADM;1.0umol/lBr-Tet+lug/mlADM for 1 hour, respectively. Thecytotoxicity effect was observed by using 3 - (4 , 5 - dimethylthi-azol - 2 - yl) - 2, 5 - diphenyltetrazolium bromide(MTT) assay in vitro, and intracellular drug concentration and the expression of Pgp were analysed with flow cytometry ( FCM) after treated with Br-Tet of different concentration combined with lug/ml ADM and different temperature. Statistical analysis depends on SAS8.0.[Result] Sensitivity of MCF-7/ADM to ADM was significantly lower than that of MCF-7.Br-Tet showed marked synergstic effects in MCF-7/ADM. The sensitivity of MCF-7/ADM to ADM increased after the treatment of Br-Tet combined with heating. P-gp expression was significantly decreased and intracellular concentration of ADM increased by exposure to the treatment. In the all conditions observed, lumol/1 Br-Tet combined with lug/ml ADM at 42℃ could reverse the multidrug resistance efficiently. [Conclusion] It is suggested that combined Br-Tet with heating could be used as a method to overcome multidrug resistance. Br-Tet showed marked synergstic effects with thermochemotherapy in MCF-7/ADM.