Reversal Of Malignant Tumor Multidrug Resistance In Clinical And Experimental Research

To search effective drug to overcome tumor mutidrug resitance (MDR), The effect of Ni-zhuan-tang(NZT) and low dose cyclosporine A(CsA) on r eversal of MDR in cancer wa~istudied. Expression of P-gp. MRD, LRP and GST in 102 advanced Non-small cell lung cancer and breast cancer pat ien ts was determined by immunohistochemistry on formalin-fixed, Paraffin-embedded tumor section. According to the result of detection, MDR positi ye patients were randomized into 3 group: NZT group and CsA group as we 11 as control group. Patients of NZT group were treated with NZT and an ticancer drug, Patients of CsA group were treaded with CsA and anticane er drug, Patients of control group and MDR negative patients were treat ed wit~h anticancer drug alone. All patients were treated with two cycle of chemotherapy at least. The response rate was 50. 0% in NZT group and 53. 8% in CsA group and 20% in control group. The response rate of NZT group and CsA group was significantly higher than of control group(P<0. 05). The clinical study also showed: NZT can improve the living quality, The weight of body and the celluar immunity function, alleviate the si de-effect of chemotherapy.We also studied the mechanism of NZT and CsA on reversal of MDR on the level of cell and gene. NZT and CsA were studied with the technique of cell culture in vitro and the method of serum pharmacology. The stu dy was carried out using human breast cancer MCF-7/ADR cells and MCF-7 cells. The cytotoxicity to cancer cells was determine with tetrazolium (MTT) assay and the expression Of P-glycoprotein were examined by flow cytometric assay. The results showed that the different concentration o f serum contained NZT and CsA as well as NZT and CsA in the dose free f ron cytotoxity could enhance the sensitivity of multidrug resistant eel ls to antiæ¢'ancer drugs in a dose-dependent way and reduced the expression of P-gp in MCF-7/ADR cells. The results mentioned above showed that NZT may be a MDR modulator of MCF7/Adr cells. One of the mechanisms can be related to depression of the P-gp expression whereby an increase of the ADM accumulation in the cells will occur.