Increased endogenous PKG I activity attenuates EGF-induced proliferation and migration of epithelial ovarian cancer via the MAPK/ERK pathway.

The type I cGMP-dependent protein kinase (PKG I) is recognized as a tumor suppressor, but its role in EGFR regulated epithelial ovarian cancer (EOC) progression remains unclear. We evaluated the in vivo and in vitro effects of activated PKG I in EGF-induced EOC cell proliferation, migration, and invasion. The expressions of EGFR and PKG I were elevated, but the activated PKG I was decreased in EOC tissues of patients and cells lines. The addition of 8-Br-cGMP, a specific PKG I activator, attenuated the EGF-induced EOC cell proliferation, migration, and invasion in vitro. Similarly, activated PKG I also attenuated EOC progression in vivo using an EOC xenograft nude mouse model. The activated PKG I interacted with EGFR, causing increased threonine (693) phosphorylation and decreased tyrosine (1068) phosphorylation of EGFR, which resulted in disrupted EGFR-SOS1-Grb2 combination. Subsequently, the cytoplasmic phosphorylation of downstream proteins (c-Raf, MEK1/2, and ERK1/2) were declined, impeding the phosphorylated ERK1/2's nucleus translocation, and this reduction of phosphorylated tyrosine (1068) EGFR and ERK1/2 were also abolished by Rp-8-Br-cGMPS. Our results suggest that the activation of PKG I attenuates EGF-induced EOC progression, and the 8-Br-cGMP-PKG I-EGFR/MEK/ERK axis might be a potential target for EOC therapy.

[Clinical efficacy of irbesartan and amiodarone in elderly patients with paroxysmal atrial fibrillation].

OBJECTIVE: To investigate the effect of combination of irbesartan and amiodarone in elderly patients with paroxysmal atrial fibrillation. METHODS: Ninety-one patients with paroxysmal atrial fibrillation were randomly divided into 2 groups: Group I (amiodarone group, n=45) and Group II (amiodarone plus Irbesartan group, n=46).After 18 month follow-up, the maintenance rate of sinus rhythm was measured in the 3rd, 6th, 9th, 12th, and 18th months, and the left atrial diameter (LAD) was measured before the treatment and 6th, 12th, and 18th months after the treatment. RESULTS: There was no difference in the maintenance rate of sinus rhythm between Group I and Group II in the 3rd month. The maintenance rate of sinus rhythm in Group I was 72.1%, 65.1%, 60.5%, and 55.8% in the 6th, 9th, 12th, and 18th months, and the rate in the Group II was 88.6%, 86.4%, 81.8%, and 79.5%. They both had significant difference (P<0.05). At 12 months after the treatment, LAD in Group I was significantly larger than that of Group II (P<0.05). CONCLUSION: The combination of irbesartan and amiodarone is more effective than amiodarone alone for sinus rhythm maintenance, and may restrain the enlargement of the left atrium.