Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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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
Hidenori AndoKiyoshi EshimaTatsuhiro Ishida
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2021 Volume 44 Issue 2 Pages 266-270


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.

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© 2021 The Pharmaceutical Society of Japan
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