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The Biological Characteristics Of Multidrug Resistance Cells And The Expression Of The Factors Associated With Apoptosis

Posted on:2003-06-27Degree:DoctorType:Dissertation
Country:ChinaCandidate:S D WangFull Text:PDF
GTID:1104360092465528Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
The research on multidrug resistance has been the hot point in cancer study for a long time. How to induce apoptosis in these never-die cell in order to cure cancer is the consistency principle of the cancer researchers. This study has investigated the biology characteristic and the key enzyme of apoptosis-caspase-3 and other factors associated with apoptosis in multidrug resistant cell and the parent cell.1. There are quite different biochemical behaviors between multidrug resistance cell and sensitive cell which are the reduction of accumulation of drug in MDR cell, the enhancement of the ability of release the toxin and the reduction of the split of DNA, and so on. In order to have a deep understanding of the multidrug resistant cell line that we established, we detected the cell survival percentage using MTT, observed the accumulation of drug in cell using fluorescent microscope, tested the expression of p-gp and CD44. Our result indicted that SGC7901/V08 was multidrug resistant, it had higher MDR index when compared with vincristine and ADR, theaccumulation of drug was low in multidrug resistant cell under fluorescent microscope, and the MDR ability of SGC7901/V08 might be associated with the expression of p-gp and EGFR.2. The gene sequence, gene expression, protein expression, protein activity of caspase-3 in mdr cell and sensitive cell. Our results indicated that the gene sequence of caspase-3 in these tow cells were same and the sequenced sequence is the same with the reported sequence. The mRNA expression of caspase-3 in the two cells were no significant difference without the administration of ADR, the mRNA expression of caspase-3 are same in mdr cell with high dose drug for long time and in sensitive cell with low dose drug for short time; the protein expression of caspase-3 in these two cells without drug had no notable diversity. The active protein piece of caspase-3 appeared in mdr cell with high dose of drug for long time, on the other hand, the active protein piece appeared in sensitive cell with low drug for 6h.3. The expression of c-fos ,bcl-2 and bax in adriamycin induced apoptosis cell. Our results implied that low dose of adr could induce apoptosis in sensitive cell, high dose of adr can induce apoptosis in mdr cell, and this process highly associated with the activity of caspase-3. When apoptosis happened, the expression of bcl-2 was decreased, the expression of bax was increased, the expression of c-fos had no change in mdr cell; the expression of bcl-2 was decreasde, the expression of bax was increased, the expression of c-fos was decreased in sensitive cell. Thus it could be seen that the apoptosis associate factors have quilt different behavior in this two cell which implied that there might be many co-factors involved in this process.
Keywords/Search Tags:tumor, multidrug resistance, gene clone, apoptosis, caspase-3, bcl-2
PDF Full Text Request
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