School of Public Health, Xinxiang Medical University, Xinxiang, 453003, China; Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing, 100084, China.
School of Public Health, Xinxiang Medical University, Xinxiang, 453003, China.
Talanta. 2022 Jun 1;243:123331. doi: 10.1016/j.talanta.2022.123331. Epub 2022 Feb 21.
The extracellular microenvironments play a key role in tumor metabolism. To online dynamic monitoring the efficacy of 7-hydroxycoumarin (7-OHC) to cells cultured on microfluidics in acidic microenvironment, we developed an integrated multi-channel chip-mass spectrometry system. This system has six drug-loading units, cell culture chamber, metabolite collection, filtration, HPLC separation and MS detection. The cells in each microchannel will be incubated with continuous flow of culture medium, metabolites will be collected by the fixed card slot, automatic sampling needle will be precise positioned and sampled. Through this new system, the 7-hydroxycoumarin-sulfonate (7-OHC-sulfonate) and 7-hydroxycoumarin-glucuronide (7-OHC-glucuronide) can be determined in real-time. The results revealed that the addition of lactic acid promoted the formation of inactive 7-OHC-sulfonate and 7-OHC-glucuronide metabolites. Besides, acidic extracellular environment amplified cancer cell proliferation, indicating the anticancer effect of 7-OHC was weakened by low extracellular pH.
细胞外微环境在肿瘤代谢中起着关键作用。为了在线动态监测 7-羟基香豆素（7-OHC）在微流控芯片酸性微环境中培养的细胞的疗效，我们开发了一种集成的多通道芯片-质谱系统。该系统有六个药物加载单元、细胞培养室、代谢物收集、过滤、HPLC 分离和 MS 检测。每个微通道中的细胞将用连续的培养基流孵育，代谢物将通过固定的插槽收集，自动采样针将精确定位和采样。通过这个新系统，可以实时测定 7-羟基香豆素-硫酸盐（7-OHC-硫酸盐）和 7-羟基香豆素-葡萄糖醛酸苷（7-OHC-葡萄糖醛酸苷）。结果表明，乳酸的添加促进了无活性的 7-OHC-硫酸盐和 7-OHC-葡萄糖醛酸苷代谢物的形成。此外，酸性细胞外环境促进了癌细胞的增殖，表明低细胞外 pH 减弱了 7-OHC 的抗癌作用。
