Sodium bicarbonate transporter NBCe1 regulates proliferation and viability of human prostate cancer cells LNCaP and PC3
| Autor: | Reda Zafar, Inyeong Choi, Eunjung Shin, Soojung Lee, Jun Ming Li |
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| Rok vydání: | 2020 |
| Předmět: |
Male
S0859 Cancer Research Cell Survival Cell Prostate cancer DU145 PC3 Cell Line Tumor LNCaP medicine Humans Cell Proliferation Sulfonamides Cell growth Chemistry Gene Expression Profiling Sodium-Bicarbonate Symporters prostate cancer cell Sodium Prostatic Neoplasms knockdown General Medicine Articles Cell cycle medicine.disease sodium bicarbonate transporter Up-Regulation Gene Expression Regulation Neoplastic medicine.anatomical_structure Sodium Bicarbonate Oncology Cell culture Tissue Array Analysis pH regulation Case-Control Studies Gene Knockdown Techniques Cancer cell Benzamides PC-3 Cells Cancer research |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 |
| Popis: | Studies on cultured cancer cells or cell lines have revealed multiple acid extrusion mechanisms and their involvement in cancer cell growth and progression. In the present study, the role of the sodium bicarbonate transporters (NBCs) in prostate cancer cell proliferation and viability was examined. qPCR revealed heterogeneous expression of five NBC isoforms in human prostate cancer cell lines LNCaP, PC3, 22RV1, C4-2, DU145, and the prostate cell line RWPE-1. In fluorescence pH measurement of LNCaP cells, which predominantly express NBCe1, Na+ and HCO3--mediated acid extrusion was identified by bath ion replacement and sensitivity to the NBC inhibitor S0859. NBCe1 knockdown using siRNA oligonucleotides decreased the number of viable cells, and pharmacological inhibition with S0859 (50 µM) resulted in a similar decrease. NBCe1 knockdown and inhibition also increased cell death, but this effect was small and slow. In PC3 cells, which express all NBC isoforms, NBCe1 knockdown decreased viable cell number and increased cell death. The effects of NBCe1 knockdown were comparable to those by S0859, indicating that NBCe1 among NBCs primarily contributes to PC3 cell proliferation and viability. S0859 inhibition also decreased the formation of cell spheres in 3D cultures. Immunohistochemistry of human prostate cancer tissue microarrays revealed NBCe1 localization to the glandular epithelial cells in prostate tissue and robust expression in acinar and duct adenocarcinoma. In conclusion, our study demonstrates that NBCe1 regulates acid extrusion in prostate cancer cells and inhibiting or abolishing this transporter decreases cancer cell proliferation. |
| Databáze: | OpenAIRE |
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