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化合物YSY01-A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,但是该化合物对人非小细胞肺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YSY01-A单用及其与顺铂联用时,对非小细胞肺癌细胞A549的体外作用,并探讨可能的分子机制。研究表明,化合物YSY01-A对A549细胞具有显著的增殖抑制作用,且与顺铂联用后显示出较强的协同作用。分子机制研究表明,化合物YSY01-A能使PI3K表达下降,Akt的磷酸化水平降低,显著增加通路负性调节蛋白PTEN的表达。与顺铂联用后,化合物YSY01-A能显著提高细胞内的铂蓄积量,并上调CTRl蛋白的表达。综上所述,化合物YSY01-A具有较好的治疗非小细胞肺癌临床前景,并且可与顺铂联用增加抗肿瘤疗效。
The compound YSY01-A is a novel proteasome inhibitor. Preliminary studies have initially shown that it has a significant anti-tumor effect. However, the study on the effect and mechanism of this compound on human non-small cell lung cancer cells remains unclear. This experiment was designed to evaluate the in vitro effects of compound YSY01-A alone and in combination with cisplatin on non-small cell lung cancer A549 cells and to explore possible molecular mechanisms. Studies have shown that compound YSY01-A on A549 cells had a significant inhibition of proliferation, and combined with cisplatin showed a strong synergistic effect. Molecular mechanism studies showed that compound YSY01-A can decrease the expression of PI3K, reduce the phosphorylation of Akt, and significantly increase the expression of PTEN, a negative regulator of the pathway. Combined with cisplatin, compound YSY01-A can significantly increase the intracellular accumulation of platinum, and up-regulate the expression of CTR1 protein. In summary, the compound YSY01-A has better clinical prospects for the treatment of non-small cell lung cancer, and cisplatin can increase antitumor efficacy.