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
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
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DOI：
10.1248/bpb.b20-00825
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发表时间：
2021-02-01
影响因子：
2
通讯作者：
Ishida, Tatsuhiro
中科院分区：
文献类型：
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作者：
Ando, Hidenori;Eshima, Kiyoshi;Ishida, Tatsuhiro
肿瘤细胞的细胞外pH（pHe）是肿瘤微环境（TME）的特征。酸性TME损害肿瘤对某些抗癌化疗的反应。在这项研究中，我们发现，每日口服柠檬酸钾钠（K/Na citrate）增加血液中的HCO 3-浓度，相应的HCO 3-浓度和尿液中的pH值的增加，并中和肿瘤的pH值。在Panc-1胰腺癌异种移植鼠模型中，酸性TME被碱性物质如HCO 3-（柠檬酸钾/钠的活性代谢物）中和，很好地增强了抗癌剂TS-1（R）（一种口服活性5-氟-尿嘧啶衍生物）的治疗效果。通过使用碱性柠檬酸钾/钠中和酸性TME是增强抗癌剂对终末期胰腺癌的治疗效果的聪明方法。
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.