Mechanism Of Resistance And Its Reversal In Tumor Cells

A major obstacle limiting the successful chemotherapy of cancer is the emergence of intrinsic or acquired drug resistance. Drug resistance may be the results of cell differentiation and malignant transformation while being one kind of physiological reactions and protective functions of cells. It is very important to understand the factors and their mechanisms involved in resistance for the extensive reverse research and clinical application in the future.Multidrug resistance gene (mdr-1) plays role in resistance to lipophilic cytotoxic compounds with different structures and functions called MDR. But it didn't provide satisfactory explanation to some resistant pheno mina in several major tumors including breast and lung. There must be mechanisms other than MDR contributing to resistance in these tumors. The elevated expression of GST- π in drug resistant cells prompted us to study its possible contribution to drug resistance.We established two ADM resistant cancer cell lines derived from human lung adenocarcinoma (GLC) and colon cancer(HR8348) respectively. We took a short term inducing protocol and the multiple clonal resistant cells have a resistant factor less than 5 , named as GLC/ADM and HR/ADM. The resistant lines showed differences from their perantal cells in chromosomes distributions, growth rates and colony forming abilities.HR/ADM showed intrinsic resistance because it was much less sensitive to ADM or VCR than GLC and positive stained by P-170 Mab, JSB-1, compared with negative staining of GLC. Southern blot indicated 3 times amplification of mdr-1 gene in HR/ADM while RT-PCR showed elevated...