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化合物YSY-01A是一种新型蛋白酶体抑制剂,前期研究已初步证实其具有显著的抗肿瘤作用,但是该化合物对人胃癌细胞的作用及相关机制研究尚不明确。本实验旨在评价化合物YSY-01A对人胃癌细胞MGC-803的体外和体内作用,并探讨可能的分子机制。体外研究表明,化合物YSY-01A对人胃癌细胞MGC-803具有显著的增殖抑制作用?体内研究表明,化合物YSY-01A单用及与5-FU联用时均可以显著地抑制裸鼠MGC-803异种移植瘤的生长,并且化合物YSY-01A与5-FU具有协同作用。分子机制研究证实,YSY-01A可以显著地抑制TNF-α和IFN诱导的NF-κB核转位,显著地下调IKK-β、IL-1β、iNOS蛋白的表达和上调COX-2蛋白的表达。综上所述,化合物YSY-01A具有较好的抗肿瘤作用,其机制与NF-κB通路相关蛋白有关。
The compound YSY-01A is a novel proteasome inhibitor. Preliminary studies have initially demonstrated that it has a significant anti-tumor effect. However, the effect of the compound on human gastric cancer cells and the related mechanisms are not yet clear. This experiment aimed to evaluate the in vitro and in vivo effects of compound YSY-01A on human gastric cancer cell line MGC-803 and to explore the possible molecular mechanisms. In vitro studies showed that compound YSY-01A could significantly inhibit the proliferation of human gastric cancer cell line MGC-803. In vivo studies showed that YSY-01A alone or in combination with 5-FU could significantly inhibit the proliferation of MGC-803 Xenografts, and the compound YSY-01A has a synergistic effect with 5-FU. Molecular mechanisms confirmed that YSY-01A could significantly inhibit the nuclear translocation of NF-κB induced by TNF-α and IFN, down-regulated the expression of IKK-β, IL-1β and iNOS and up-regulated the expression of COX-2. In summary, the compound YSY-01A has a good anti-tumor effect, and its mechanism and NF-κB pathway-related proteins.