Neutralization of Acidic Tumor Microenvironment (TME) with Daily Oral Dosing of Sodium Potassium Citrate (K/Na Citrate) Increases Therapeutic Effect of Anti-cancer Agent in Pancreatic Cancer Xenograft Mice Model

• Published in: Biological & pharmaceutical bulletin Vol. 44; no. 2; pp. 266 - 270
• Main Authors: Ando, Hidenori, Eshima, Kiyoshi, Ishida, Tatsuhiro
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.02.2021; Japan Science and Technology Agency
• Subjects: acidic extracellular pH; Animal models; Antitumor agents; cancer chemotherapy; Citric acid; Metabolites; Pancreatic cancer; Potassium; sodium potassium citrate; Tumor cells; Tumor microenvironment; tumor microenvironment (TME); Tumors; Uracil; Xenografts; acidic extracellular pH; pancreatic cancer; tumor microenvironment (TME); sodium potassium citrate; cancer chemotherapy
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b20-00825

Extracellular pH (pHe) of tumor cells is characteristic of tumor microenvironment (TME). Acidic TME impairs the responses of tumors to some anti-cancer chemotherapies. In this study, we showed that daily oral dosing of sodium potassium citrate (K/Na citrate) increased blood HCO3− concentrations, corresponding to increase of HCO3− concentrations and pHs in urine, and neutralized the tumor pHe. Neutralization of acidic TME by alkaline substance like HCO3−, an active metabolite of K/Na citrate, well potentiated the therapeutic effect of anticancer agent TS-1®, an orally active 5-fuluoro-uracil derivative, in Panc-1 pancreatic cancer-xenograft murine model. Neutralization of acidic TME by using an alkaline K/Na citrate is a smart approach for enhancement of the therapeutic effects of anticancer agents for pancreatic cancer in the end stage.