[Effect of PKC inhibitor on P-gp expression and drug-resistance in MGC803 cells].
OBJECTIVE
It is showed that there is close relationship between multidrug resistance (MDR) and protein kinase C signal transduction system, but the mechanism remains unclarified. The aim of this study was to investigate the correlation between protein kinase C (PKC) signal transduction system and mdr1 gene in human gastric cancer cell line through studying the effect of vincristine (VCR) and a selective inhibitor of PKC, myr-psiPKC on MGC803 cells.


METHODS
Western blot analysis was used to analyze the expression of P-glycoprotein (P-gp), which was encoded by mdr1, in transient VCR induced MGC803 cells, which were treated with or without myr-psiPKC. Cell cycle analysis was performed using flow cytometry and MTT assay was used to investigate the drug susceptibility of MGC803 cells which were exposed to VCR with or without myr-psiPKC.


RESULTS
High level of P-gp expression was detected in the MGC803 cells after transient exposure to VCR, and its expression was down-regulated when the same VCR induced MGC803 cell line was incubated with myr-psiPKC. FCM results indicated that more MGC803 cells showed significantly higher level of apoptotic phenotype when treated with VCR and myr-psiPKC (ratio 31.23%), than those treated with only VCR (ratio 18.42%). The IC(50) (284.0+/-13.2 ng/ml) to VCR of MGC803 cells pretreated with VCR exhibited 2.24-fold of negative control group (127.0+/-17.6 ng/ml) and 1.33-fold of the group (212.0+/-30.4 ng/ml) treated with myr-psiPKC.


CONCLUSIONS
The expression of P-gp can be induced by transient exposure to VCR and this induction can be inhibited by myr-psiPKC, which blocks the activity of PKCalpha and beta. PKC signal transduction system may play certain roles in modulating mdr1 expression in gastric cancer.
Chen
Bo
B
Department of Surgical Oncology, The First Affiliated Hospital, China Medical University, Shenyang, 110001, PR China. chbyxlpnt@yahoo.com.cn
Jin
Feng
F
Lu
Xiang-Lan
XL
Wang
Ping-Ping
PP
Liu
Yun-Peng
YP
Wang
Shu-Bao
SB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D014750:Vincristine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004791:Enzyme Inhibitors; D014750:Vincristine; D011493:Protein Kinase C