Application of the ERK signaling pathway inhibitor PD98059 in long-term in vivo experiments

Abstract

ABSTRACT. The aim of this study was to explore methods by which the ERK signaling pathway inhibitor PD98059 (PD) could be used in long-term in vivo experiments. Forty healthy New Zealand rabbits were randomly divided into blank control, model control, PD low-dose, PD high-dose, PD blank, dimethyl sulfoxide (DMSO) control, DMSO blank, and positive control groups. The corresponding treatments were administered to each experimental group over the course of four weeks, after which, total ERK1/2 and ERK5 protein levels, protein phosphorylation, and gene expression were measured in myocardial tissues. Treatment of rabbits with Adriamycin (doxorubicin) resulted in the significant overall differences in ERK1/2 and ERK5 phosphorylation (P < 0.05). Compared with the model control group, changes in phosphorylated ERK1/2 and phosphorylated ERK5 were lowest in the PD high-dose group (P < 0.05). No significant differences in total protein and mRNA levels of myocardial ERK1/2 and ERK5 were detected between the groups after four weeks (P > 0.05). Continuous intravenous injection of PD98059 significantly reduced phosphorylation of ERK1/2 X.Y. Chen et al. 18326©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 18325-18333 (2015) and that of ERK5. In conclusion, Adriamycin-induced myocardiopathy and abnormal ERK signaling might constitute a valuable model foruse in long-term experiments. These methods may provide a theoretical basis for related in vivo studies of long duration.

KIF15 promotes pancreatic cancer proliferation via the MEK–ERK signalling pathway

“…The incision was then closed with sutures. PD98059 was diluted in dimethyl sulfoxide (DMSO) solution to a concentration of 1.0 mg ml −1 , and from day 1 onward, mice were subcutaneously injected with 40  μ g kg −1 ·per day (Chen et al , 2015). All mice were routinely weighed and checked for signs of distress.…”

Cisplatin effect on head and neck squamous cell carcinoma cells is modulated by ERK1/2 protein kinases

“…Tumor cells were incubated for 6, 24 or 48 h either in the presence of the drugs (CisPt and/or CRM) or vehicle control (DMSO ≤0.1%). For inhibition studies of ERK1/2 function, the cells were pre-incubated for 2 h with 25 µM PD98059 as previously reported (40). The treated tumor cells were used to determine cell proliferation, FISH, apoptosis and conserved as cell pellets at −80°C in order to obtain cell lysates used in ELISA assays.…”