0000000000724792
AUTHOR
Manfred Volm
Overcoming of P-glycoprotein-mediated multidrug resistance of tumors in vivo by drug combinations
Summary Inhibition of P-glycoprotein represents an attractive possibility to modulate resistance of cancer cells to anticancer drugs. One major strategy to overcome P-glycoprotein-mediated multidrug resistance (MDR) of tumors is to increase intracellular concentrations of anticancer drugs. This can be achieved by blocking of P-glycoprotein-mediated drug efflux using synthetic or natural small molecules or monoclonal antibodies, which bind to various parts of the efflux channel. Another possibility to increase intracellular drug concentrations can be reached by nanoparticles. A further major strategy to overcome MDR involves the downregulation of P-glycoprotein expression either by therapeut…
O6-methylguanine-DNA methyltransferase activity and sensitivity to cyclophosphamide and cisplatin in human lung tumor xenografts
The DNA repair protein O6-methylguanine-DNA methyl-transferase (MGMT) is a main determinant of resistance of cells to the cytostatic effects of O6-alkylguanine-generating alkylating agents. The purpose of our study was to assay MGMT activity in cells of lung cancers and to correlate MGMT levels with chemotherapy response to cyclophosphamide (CTX) and cisplatin (DDP). MGMT levels were determined in 14 human lung tumor xenografts. There was a wide variation of MGMT expression in these tumors, ranging from 10 to 984 fmol/mg protein. There was also a wide range in the sensitivity of the xenografts to CTX and DDP, as measured by specific growth delay. When the MGMT levels of the different xenogr…