[Mechanism of reversal of multidrug resistance in human renal carcinoma cells by protein kinase C inhibitor].
摘要
OBJECTIVE: To explore the mechanism of reversal of multidrug resistance in renal carcinoma cells by protein kinase C inhibitor. METHODS: RT-PCR, Western blot and inverted fluorescent microscopy were used to determine the expression of PKCalpha and MDR related gene MDR1, MRP1, LRP in RCC cells transferred by PKCalpha cDNA. Also effects of activator and inhibitor of PKC in combination with adriamycin on multidrug resistance in RCC cells were evaluated by MTT. RESULTS: The results of semi-quantitative RT-PCR analysis showed that the expression level of MDR1 was higher in RCC cells transferred by PKCalpha cDNA than in RCC cells, the reversal effectiveness of PKC inhibitors in combination with adriamycin (ADM) was apparently favorable. IC(50) of ADM in 786 - 0 cells was 7.8015e(-7) (5.7046e(-7) to 1.0669e(-6)); IC(50) of ADM in PKCalpha/786 - 0 cells was 1.6588e(-6) (1.1621e(-6) to 2.3677e(-6)); IC(50) of ADM in combination with PMA in PKCalpha/786 - 0 cells was 2.6794e(-6) (2.0521e(-6) to 3.4983e(-6)); IC(50) of ADM in combination with calphostin C in PKCalpha/786 - 0 cells was 9.2506e(-8) (5.9337e(-8) to 1.4422e(-7)). CONCLUSION: PKC inhibitors can reverse multidrug resistance in renal carcinoma cells in vitro via changes of expression of MDR1.