Research On Molecule-mechanism Of Lung Cancer Multidrug Resistance

The malignant tumor is one of the severe diseases which are harmful to the health of human beings. The investigation of the death causes shows that the death rate of lung cancer is more rapidly increasing in last twenty years, Now lung cancer is usually treated with local measures including surgery, chemotherapy, radiotherapy and immunotherapy. Chemotherapy as a systemic therapy means can not be replaced by surgery and radiotherapy as for the therapies of malignant tumors. But tumor cell's drug resistance, especially its multidrug resistance (MDR), results in the default of clinical chemotherapy. The mechanism of tumor multidrug resistance is very complex, which is concerned with polygene and multipath way. Including:①The overexpression of MDR gene and Permeability-glycoprotein(P-gp).②The overexpression of Multidrug resistance associated gene (MRP)and Multidrug resistance associated protein.③The overexpression of lung cancer resistance-related gene and lung cancer resistance-related protein(LRP).④The overexpression of glutathione s-transferase pi(GST-π).⑤The reduction content of DNA TopoisOmerase II(TopoII).⑥The increase of the tumor cells capacity of repairing damage of DNA and antiapoptosis,et al.To avoid acquired multidrug resistance caused by MDR drug we can forecast the drug resistance of tumor and realize individualized chemotherapy of patients. There are a lot of literatures relating to this aspect, and the factors discussed are single in these literatures. Furthermore, there are contradictions among these literatures. Therefore, we have chosen lung carcinoma as research object to realize sufficiently the multidrug resistance of lung carcinoma. Including: (1)To detecte the drug sensitivity of lung cancer tissue in vivo by MTT to choose the appropriate experimental conditions to treat the NSCLC and find sensitive drug. (2)To observe the mRNA and protein expression of P-gp, MRP, LRP, GST-π, Topo-II, P53 and Bcl-2 and ras and evaluated the relationship of them. (3)To observe the relationship between the protein expression of P-gp, MRP, LRP, GST-π, TopoII, p53 and Bcl-2 and pharmic sensitivity of lung cancer cell in vivo. (4)To study the relativity of the lung cancer tissue and pharmic sensitivity experiment of peripheral blood monocyte.1 Detection of chemosensitivity of human lung cancer cells in vitro Selection of experiment condition of NSCLC drug sensibility Selection of drug concentrations of NSCLC drug sensibility.25 cases of human NSCLC pro-generation cells were treated with 8 chemotherapeutic drugs with different concentrations, and the inhibitory rates to neoplasm cells were detected by MTT assay. Drug concentration (1C) of experiment in vitro was 50×D／5000×2×103 μg/ml. According to this concentration, 10 times dilution and concentration were performed as other two concentrations. So the experiment was divided into three groups: ①0.1C group；②1C group；③10C group。The results were as follows: 1.1.1.1 When the testing drug concentration was 0.1C, only MMC and 5-Fu had chemosensitivities；However, when the testing drug concentration was increased to 1C or 10C,chemosensitive drugs were added to five or four. It was demonstrated that improved testing drug concentration can increase their ability to inhibit neoplasm cells. But moderate sensitivity drugs, whose inhibitory rates were more than 50%, were MMC, CBDCA and CDDP. There was no difference in drugs species. 1.1.1.2 Comparison of inhibitory rates to lung cancer cells with same drug in different concentrations: Compared with 0.1C group, in the 1C group, all drugs had the increasing tendency except that 5-Fu had the decreasing tendency. Significant difference could be seen among CDDP, CBDCA and MTX(P<0.05)； Compared with 1C group, in the 10C group, ADM, CDDP, VCR and MTX had the increasing tendency, while CBDCA, MMC, 5-Fu and Vp-16 had the decreasing tendency. 5-Fu had the obviously decreasing tendency(P<0.05). The results illustrated that the concentration of chemosensitivity of NSCLC cells with...