Autor: |
Vázquez-Sánchez AY; Department of Pharmacology, Center for Research and Advanced Studies of The National Polytechnic Institute, Mexico City 07360, Mexico., Hinojosa LM; Service of Dysplasia, Gynecology and Obstetrics, 'Dr Manuel Gea González' Hospital General, Mexico City 14080, Mexico., Parraguirre-Martínez S; Division of Anatomical Pathology, 'Dr Manuel Gea González' Hospital General, Mexico City 14080, Mexico., González A; Service of Colposcopy, Instituto Nacional de Cancerología, Mexico City 14080, Mexico., Morales F; Medical Oncology, Instituto Nacional de Cancerología, Mexico City 14080, Mexico., Montalvo G; Service of Gynecology, Instituto Nacional de Cancerología, Mexico City 14080, Mexico., Vera E; Department of Pharmacology, Center for Research and Advanced Studies of The National Polytechnic Institute, Mexico City 07360, Mexico., Hernández-Gallegos E; Department of Pharmacology, Center for Research and Advanced Studies of The National Polytechnic Institute, Mexico City 07360, Mexico., Camacho J; Department of Pharmacology, Center for Research and Advanced Studies of The National Polytechnic Institute, Mexico City 07360, Mexico. |
Abstrakt: |
Various ion channels, including ATP-sensitive potassium (K ATP ) channels, are expressed in cancer and have been suggested as potential tumor markers and therapeutic targets. K ATP channels are composed of at least two types of subunit, an inwardly rectifying K + channel (Kir6.x) and a sulfonylurea receptor (SUR). However, the association between K ATP channels and cervical cancer remains elusive. The present study determined that the Kir6.2, SUR1 and SUR2 subunits are expressed in cervical cancer cell lines and/or human biopsies. The potential association of subunit expression with tumor differentiation and invasion was analyzed. The effect of the K ATP channel blocker glibenclamide on the proliferation of cervical cancer cell lines was also studied. Five cervical cancer cell lines, two primary cultures of cervical cancer cells, one normal keratinocyte cell line and 74 human biopsies were used in the experiments. The mRNA and protein levels of the Kir6.2 subunit were assessed by reverse transcription-polymerase chain reaction and immunochemistry, respectively. Cell proliferation was evaluated by MTT assay. Kir6.2 subunit overexpression compared with control, was observed in some cervical cancer cell lines and cervical tumor tissues. Additionally, increased K ATP channel expression was observed in high-grade, poorly differentiated and invasive human cervical cancer biopsies. Kir6.2 subunit expression was not observed in the majority of the non-cancerous cervical tissues. The effect of the K ATP channel blocker glibenclamide on the proliferation of five different cervical cancer cell lines was studied, revealing that as Kir6.2 mRNA expression increased, the inhibitory effect of glibenclamide also increased. The results of the present study suggest, for the first time to the best of our knowledge, that the K ATP channel subunits, Kir6.2 and SUR2, could potentially represent tools for diagnosing and treating cervical cancer. |