Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 44, Issue 2, Pages 266-270Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b20-00825
Keywords
acidic extracellular pH; tumor microenvironment (TME); sodium potassium citrate; cancer chemotherapy; pancreatic cancer
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Funding
- Japan Society for the Promotion of Science [19K16415]
- Grants-in-Aid for Scientific Research [19K16415] Funding Source: KAKEN
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The study demonstrated that oral administration of sodium potassium citrate can neutralize the pH of tumor microenvironment, enhancing the therapeutic effects of anticancer agents for pancreatic cancer.
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 (R), 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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