Effect of mitogen-activated protein kinase signal transduction pathway on multidrug resistance induced by vincristine in gastric cancer cell line MGC803.
OBJECTIVE
To investigate the correlation between mitogen-activated protein kinase (MAPK) signal transduction pathway and multidrug resistance (MDR) in MGC803 cells.


METHODS
Western blot was used to analyze the expression of MDR associated gene in transient vincristine (VCR) induced MGC803 cells, which were treated with or without the specific inhibitor of MAPK, PD098059. Morphologic analysis of the cells treated by VCR with or without PD098059 was determined by Wright-Giemsa staining. The cell cycle analysis was performed by using flow cytometric assay and the drug sensitivity of MGC803 cells which were exposed to VCR with or without PD098059 was tested by using MTT assay.


RESULTS
Transient exposure to VCR induced P-gp but not MRP1 or GST-pi expression in MGC803 cells and the expression of P-gp was inhibited by PD098059. Apoptotic bodies were found in the cells treated with VCR or VCR+PD098059. FCM results indicated that more MGC803 cells showed apoptotic phenotype when treated by VCR and PD098059 (rate: 31.23%) than treated by VCR only (rate: 18.42%) (P<0.05). The IC(50) (284+/-13.2 mug/L) of MGC803 cells pretreated with VCR was 2.24-fold as that of negative control group (127+/-17.6 mug/L) and 1.48-fold as that of the group treated with PD098059 (191+/-27.9 mug/L).


CONCLUSIONS
This study shows that the expression of P-gp can be induced by transient exposure to VCR and this induction can be prevented by PD098059, which can block the activity of MAPK. MAPK signal transduction pathway may play some roles in modulating MDR1 expression in gastric cancer.
Chen
Bo
B
Department of Surgical Oncology, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China. chbyxl@163.com
Jin
Feng
F
Lu
Ping
P
Lu
Xiang-Lan
XL
Wang
Ping-Ping
PP
Liu
Yun-Peng
YP
Yao
Fan
F
Wang
Shu-Bao
SB
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000473:pathology / Q000503:physiopathology*; D014750:Vincristine / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D020928:Mitogen-Activated Protein Kinases