[Mechanism of reversal of multidrug resistance in human renal carcinoma cells by protein kinase C inhibitor].
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)).


CONCLUSIONS
PKC inhibitors can reverse multidrug resistance in renal carcinoma cells in vitro via changes of expression of MDR1.
Liu
Tao
T
Department of Urology, First Affiliated Hospital, Medical University of China, Shenyang 110001, China.
Kong
Chui-ze
CZ
Bi
Jian-bin
JB
Liu
Ge-fei
GF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005822:Genetic Vectors; D006801:Humans; D020128:Inhibitory Concentration 50; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D018076:DNA, Complementary; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009281:Naphthalenes; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D013755:Tetradecanoylphorbol Acetate; C061465:calphostin complex; C421109:multidrug resistance-associated protein 1