Department of Biomedicine, Aarhus University, Ole Worms Allé 3, Building 1170, DK-8000 Aarhus C, Denmark.
Regional Hospital Randers, Skovlyvej 15, DK-8930 Randers, Denmark.
Biomed Res Int. 2019 Jan 29;2019:3702783. doi: 10.1155/2019/3702783. eCollection 2019.
Increased metabolism accelerates local acid production in cancer tissue. The mechanisms eliminating acidic waste products from human colon cancer tissue represent promising therapeutic targets for pharmacological manipulation in order to improve prognosis for the increasing number of patients with colon cancer. We sampled biopsies of human colonic adenocarcinomas and matched normal colon tissue from patients undergoing colon cancer surgery. We measured steady-state intracellular pH and rates of net acid extrusion in freshly isolated human colonic crypts based on fluorescence microscopy. Net acid extrusion was almost entirely (>95%) Na-dependent. The capacity for net acid extrusion was increased and steady-state intracellular pH elevated around 0.5 in crypts from colon cancer tissue compared with normal colon tissue irrespective of whether they were investigated in the presence or absence of CO/HCO . The accelerated net acid extrusion from the human colon cancer tissue was sensitive to the Na/H-exchange inhibitor cariporide. We conclude that enhanced net acid extrusion via Na/H-exchange elevates intracellular pH in human colon cancer tissue.
新陈代谢的增加会加速癌症组织中的局部酸生成。从人类结肠癌组织中清除酸性废物的机制代表了有前途的治疗靶点，可通过药理学手段进行操纵，以改善越来越多的结肠癌患者的预后。我们从接受结肠癌手术的患者中取样了人类结肠腺癌的活检组织和匹配的正常结肠组织。我们根据荧光显微镜测量了新鲜分离的人结肠隐窝中的稳态细胞内 pH 值和净酸外排率。净酸外排几乎完全（>95%）依赖于 Na。与正常结肠组织相比，无论是否存在 CO/HCO，来自结肠癌组织的隐窝中的净酸外排能力增加，稳态细胞内 pH 值升高约 0.5。从人结肠癌组织中加速的净酸外排对 Na/H 交换抑制剂 cariporide 敏感。我们的结论是，通过 Na/H 交换增强的净酸外排会升高人结肠癌组织中的细胞内 pH 值。
