Effects of MEK signaling inhibitor on the growth of human pacreatic cancer cell lines and the expression of cell cyde associated genes
10.3760/cma.j.issn.1674-1935.2011.04.009
- VernacularTitle:MEK通路抑制剂对人胰腺癌细胞生长及细胞周期相关抑癌基因表达的影响
- Author:
Xia WANG
;
Hui WANG
;
Nan JIANG
;
Sanhong LIANG
;
Wen Lü
;
Xiao ZHANG
;
Xiaofeng ZHANG
- Publication Type:Journal Article
- Keywords:
Pancreas;
Tunor cell line;
MEK inhibitor;
Cell cycle;
DNA methyltransferase;
Tumor suppressor genes
- From:
Chinese Journal of Pancreatology
2011;11(4):259-262
- CountryChina
- Language:Chinese
-
Abstract:
Objective To examine the effects of the MEK inhibitor on human pancreatic cancer cells, and to explore the molecular mechanisms. Methods Human pancreatic cancer cell lines CFPANC1, PANC1 and MiaPaCa2 were treated with MEK inhibitor PD98059 or DMSO, the sensitivity was analyzed by an MTT assay, and cell cycle distribution was evaluated by flow cytometry( FCM), The transcriptional level and protein expression of tumor suppressor genes were detected by real-time RT-PCR and western blot respectively. DNA methyltransferase (Dnmt)1, 3a and 3b were also assayed by western blot, The methylation status of the promoter of the p16INK4A gene was assayed by methylation-specific PCR (MSP). Results PD98059 inhibited to various degrees the growth of three pancreatic cancer cell lines, accompanied by G0-G1 cell cycle arrest. PD98059 up-regulated the expression of p16INK4a, p21WAF1, p27KIP1 mRNA, demethylated the hypermethylation status of p16INK4a gene promoter, and decreased Dnmtl and Dnmt3b in CFPANC1 and PANC1 cell lines. PD98059 only increased the expression of p27KIP1, while the changes of p16INK4a, p21WAF1 and Dnmt were less marked in MiaPaCa2 cell line. Conclusions MEK inhibitor PD98059 down-regulate the activation of Dnmt and up-regulate tumor supress genes, along with the inhibition of cell proliferation and cell cycle progression.
