Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190, China.
University of Chinese Academy of Sciences , Beijing 100049, China.
Anal Chem. 2016 Aug 16;88(16):8309-14. doi: 10.1021/acs.analchem.6b02231. Epub 2016 Jul 29.
Dipeptide peptidase IV (DPPIV) and fibroblast activation protein (FAP) are isoenzymes. Evidence shows that DPPIV is related to antitumor immunity, and FAP may be a drug target in cancer therapy, making it seem that the two enzymes might have a synergistic role during the proliferation of cancer cells. Surprisingly, herein, we find an adverse action of DPPIV and FAP in the proliferation process by analyzing their changes with two tailor-made ultrasensitive fluorescent probes. First, the up-regulation of DPPIV and down-regulation of FAP in cancer cells under the stimulation of genistein are detected. Then, we find that MGC803 cells with a higher FAP but lower DPPIV level than SGC7901 cells exhibit a faster proliferation rate. Importantly, inhibiting the DPPIV expression with siRNA increases the proliferation rate of MGC803 cells, whereas the FAP inhibition decreases the rate. These findings suggest that the two enzymes play an adverse role during the proliferation of cancer cells, which provides us a new viewpoint for cancer studies.
二肽基肽酶 IV（DPPIV）和成纤维细胞激活蛋白（FAP）是同工酶。有证据表明，DPPIV 与抗肿瘤免疫有关，而 FAP 可能是癌症治疗中的药物靶点，这表明这两种酶在癌细胞增殖过程中可能具有协同作用。令人惊讶的是，在此，我们通过分析两种定制的超灵敏荧光探针的变化，发现 DPPIV 和 FAP 在增殖过程中具有不利作用。首先，检测到在染料木黄酮刺激下癌细胞中 DPPIV 的上调和 FAP 的下调。然后，我们发现与 SGC7901 细胞相比，具有更高 FAP 但更低 DPPIV 水平的 MGC803 细胞表现出更快的增殖速率。重要的是，用 siRNA 抑制 DPPIV 的表达会增加 MGC803 细胞的增殖速率，而 FAP 抑制则会降低速率。这些发现表明，这两种酶在癌细胞的增殖过程中起不利作用，为癌症研究提供了新的视角。
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