RESUMO
PURPOSE: Aberrant expression of potassium (K(+)) channels contributes to cancer cell proliferation and apoptosis, and K(+) channel blockers can inhibit cell proliferation. TREK-1 and -2 belong to the two-pore domain (K2P) superfamily. We report TREK-1 and -2 expression in ovarian cancer and normal ovaries, and the effects of TREK-1 modulators on cell proliferation and apoptosis. METHODS: The cellular localisation of TREK-1 and -2 was investigated by immunofluorescence in SKOV-3 and OVCAR-3 cell lines and in cultured ovarian surface epithelium and cancer. Channel expression in normal ovaries and cancer was quantified by western blotting. Immunohistochemical analysis demonstrated the association between channel expression and disease prognosis, stage, and grade. TREK-1 modulation of cell proliferation in the cell lines was investigated with the MTS-assay and the effect on apoptosis determined using flow cytometry. RESULTS: Expression was identified in both cell lines, ovarian cancer (n = 22) and normal ovaries (n = 6). IHC demonstrated positive staining for TREK-1 and -2 in 95.7 % of tumours (n = 69) and 100 % of normal ovaries (n = 9). A reduction in cell proliferation (P < 0.05) was demonstrated at 96 h in SKOV-3 and OVCAR-3 cells incubated TREK-1 modulating agents. Curcumin caused a significant reduction in early apoptosis in SKOV-3 (P < 0.001) and OVCAR-3 (P < 0.0001) cells and a significant increase in late apoptosis in SKOV-3 (P < 0.01) and OVCAR-3 cells (P < 0.0001). CONCLUSIONS: TREK-1 and -2 are expressed in normal ovaries and ovarian cancer. TREK-1 modulators have a significant effect on cell proliferation and apoptosis. We propose investigation of the therapeutic potential of TREK-1 blockers is warranted.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Ovarianas/patologia , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Curcumina/farmacologia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Citometria de Fluxo , Imunofluorescência , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Prognóstico , Taxa de SobrevidaRESUMO
PIP: Obstetrical outcome of a series of 226 primigravid Jamaican teenagers, less than 16 years old, was evaluated. All of the study subjects delivered at the University Hospital, Kingston, Jamaica, and their obstetrical outcomes were compared with the outcomes of older primigravidas delivering at the same institution. Incidence of preeclampsia was lower among the teenagers (8.4%) vs. older patients (9.8%). Incidence of antepartum hemorrhage was .9% in the teenage group vs. 3% among the older women. Spontaneous premature rupture also occurred less frequently among the teenagers (1.8%) vs. the older women (2.4%). 15.5% of older women suffered from anemia and so did the same percentage of teenagers. Postpartum hemorrhage had a higher incidence among the teenagers (12.8%) compared with the older women (9.3%). A low operative delivery rate was associated with a low incidence of fetal distress and babies with good Apgar scores among the teenagers. This overall good obstetrical performance is attributed to better antenatal care among the teenage mothers.^ieng