engleski

Downregulation of nm23-H1 increases sensitivity of CAL 27 cells to cytostatics

The nm23 gene family consists of 8 members in humans (nm23H1-H8). The protein products of nm23-H1 and nm23-H2 are subunits of nucleoside diphosphate kinase (NDPK). Among its ability to transfer the terminal phosphate from ATP to NDPs, the Nm23/NDPK has several other distinct functions in the cell that affect different physiological processes including its involvement in various forms of cell death. To enlighten the possible role of nm23-H1 in cell death we developed a model system which consists of stably transfected CAL 27 cells that have ether overexspressed or silenced nm23-H1. We preformed a preliminary screen using MTT test to identify the cytotoxic effect of various agents on CAL 27 cells. Cells were treated with camptothecin, etoposide, cisplatin, doxorubicin and epirubicin. The LC50 values were used to treat the CAL 27 transfectants and control cells. Results show that downregulation of nm23- H1 considerably increases (p 0, 05, ANOVA test) the rate of cell death after treatment with all citotoxic agents, compared to control cells. In cells overexpressing nm23-H1 the citotoxicity of all agents is comparable to CAL 27 (p 0, 05, ANOVA test), showing slightly increased resistance in nm23-H1 overexpressing clones in a dose dependent manner. It seems that nm23-H1 downregulation might increase cell susceptibility to cell death mediated by aforementioned cytostatics. Since they are preliminary, these results need further evaluation which will define our future experiments.

nm23 ; Cal27 ; citostatics

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