In vivo dual targeting of the oncogenic Ether-à-go-go-1 potassium channel by calcitriol and astemizole results in enhanced antineoplastic effects in breast tumors
| Autor: | Rocío García-Becerra, Maŕa J Ibarra-Sánchez, Octavio Villanueva, Nancy Santos-Martínez, Armando Gamboa-Domínguez, David Barrera, David Ordaz-Rosado, Janice García-Quiroz, Euclides Avila, Javier Camacho, Fernando Larrea, José Esparza-López, Ali Halhali, Lorenza Díaz |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Calcitriol medicine.medical_treatment Mice Nude Antineoplastic Agents Breast Neoplasms Pharmacology medicine.disease_cause Calcitriol receptor Targeted therapy Mice Breast cancer In vivo Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Genetics Animals Humans Vitamin D EAG1 biology business.industry Drug Synergism Astemizole medicine.disease Ether-A-Go-Go Potassium Channels Oncology Vitamin D receptor Ki-67 biology.protein Female business Carcinogenesis Neoplasm Transplantation medicine.drug Research Article |
| Zdroj: | BMC Cancer |
| ISSN: | 1471-2407 |
| Popis: | Background The oncogenic ether-à-go-go-1 potassium channel (EAG1) activity and expression are necessary for cell cycle progression and tumorigenesis. The active vitamin D metabolite, calcitriol, and astemizole, a promising antineoplastic drug, target EAG1 by inhibiting its expression and blocking ion currents, respectively. We have previously shown a synergistic antiproliferative effect of calcitriol and astemizole in breast cancer cells in vitro, but the effect of this dual therapy in vivo has not been studied. Methods In the present study, we explored the combined antineoplastic effect of both drugs in vivo using mice xenografted with the human breast cancer cell line T-47D and a primary breast cancer-derived cell culture (MBCDF). Tumor-bearing athymic female mice were treated with oral astemizole (50 mg/kg/day) and/or intraperitoneal injections of calcitriol (0.03 μg/g body weight twice a week) during 3 weeks. Tumor sizes were measured thrice weekly. For mechanistic insights, we studied EAG1 expression by qPCR and Western blot. The expression of Ki-67 and the relative tumor volume were used as indicators of therapeutic efficacy. Results Compared to untreated controls, astemizole and calcitriol significantly reduced, while the coadministration of both drugs further suppressed, tumor growth (P |
| Databáze: | OpenAIRE |
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