title: Intermediate-Conductance-Ca2-Activated K Channel IKCa1 Is Upregulated and Promotes Cell Proliferation in Cervical Cancer
abstract: BACKGROUND Accumulating data point to intermediate-conductance calcium-activated potassium channel (IKCa1) as a key player in controlling cell cycle progression and proliferation of human cancer cells. However, the role that IKCa1 plays in the growth of human cervical cancer cells is largely unexplored. MATERIAL AND METHODS In this study, Western blot analysis, immunohistochemical staining, and RT-PCR were first used for IKCa1protein and gene expression assays in cervical cancer tissues and HeLa cells. Then, IKCa1 channel blocker and siRNA were employed to inhibit the functionality of IKCa1 and downregulate gene expression in HeLa cells, respectively. After these treatments, we examined the level of cell proliferation by MTT method and measured IKCa1 currents by conventional whole-cell patch clamp technique. Cell apoptosis was assessed using the Annexin V-FITC/Propidium Iodide (PI) double-staining apoptosis detection kit. RESULTS We demonstrated that IKCa1 mRNA and protein are preferentially expressed in cervical cancer tissues and HeLa cells. We also showed that the IKCa1 channel blocker, clotrimazole, and IKCa1 channel siRNA can be used to suppress cervical cancer cell proliferation and decrease IKCa1 channel current. IKCa1 downregulation by specific siRNAs induced a significant increase in the proportion of apoptotic cells in HeLa cells. CONCLUSIONS IKCa1 is overexpressed in cervical cancer tissues, and IKCa1 upregulation in cervical cancer cell linea enhances cell proliferation, partly by reducing the proportion of apoptotic cells.
authors.affiliation: Department of Gynaecology and Obstetrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Gynaecology and Obstetrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Ping
authors.initials: P
authors.lastname: Zhan
authors.affiliation: Department of Gynaecology and Obstetrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Dan
authors.initials: D
authors.lastname: Nie
authors.affiliation: Department of Gynaecology and Obstetrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Lingye
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Gynaecology and Obstetrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Hairui
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Gynaecology and Obstetrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Lanyang
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Gynaecology and Obstetrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
authors.forename: Xiguang
authors.initials: X
authors.lastname: Mao
mesh_terms: D000328:Adult; D002121:Calcium Channel Blockers / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D003022:Clotrimazole / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D002121:Calcium Channel Blockers; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D012333:RNA, Messenger; D003022:Clotrimazole