Zhang Junli, Liu Xiangqi, Zhang Guoying, Wu Junling, Liu Zhongfang, Liu Chuanguo, Wang Hui, Miao Shuxin, Deng Lei, Cao Kuan, Shang Miwei, Zhu Qingjun, Sun Peng
Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.
Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China.
Front Pharmacol. 2023 Jul 18;14:1148171. doi: 10.3389/fphar.2023.1148171. eCollection 2023.
Non-small cell lung cancer (NSCLC) is a common pathological type of lung cancer, which has a serious impact on human life, health, psychology and life. At present, chemotherapy, targeted therapy and other methods commonly used in clinic are prone to drug resistance and toxic side effects. Natural extracts of traditional Chinese medicine (TCM) have attracted wide attention in cancer treatment because of their small toxic and side effects. Kaempferol is a flavonoid from natural plants, which has been proved to have anticancer properties in many cancers such as lung cancer, but the exact molecular mechanism is still unclear. Therefore, on the basis of experiments, we used network pharmacology and molecular docking methods to study the potential mechanism of kaempferol in the treatment of non-small cell lung cancer. The target of kaempferol was obtained from the public database (PharmMapper, Swiss target prediction), and the target of non-small cell lung cancer was obtained from the disease database (Genecards and TTD). At the same time, we collected gene chips GSE32863 and GSE75037 in conjunction with GEO database to obtain differential genes. By drawing Venn diagram, we get the intersection target of kaempferol and NSCLC. Through enrichment analysis, PI3K/AKT is identified as the possible key signal pathway. PIK3R1, AKT1, EGFR and IGF1R were selected as key targets by topological analysis and molecular docking, and the four key genes were further verified by analyzing the gene and protein expression of key targets. These findings provide a direction for further research of kaempferol in the treatment of NSCLC.
非小细胞肺癌(NSCLC)是肺癌的一种常见病理类型,对人类的生命、健康、心理和生活都有严重影响。目前,临床上常用的化疗、靶向治疗等方法容易产生耐药性和毒副作用。中药天然提取物因其毒副作用小而在癌症治疗中受到广泛关注。山奈酚是一种来自天然植物的黄酮类化合物,已被证明在肺癌等多种癌症中具有抗癌特性,但其确切的分子机制仍不清楚。因此,在实验的基础上,我们采用网络药理学和分子对接方法研究山奈酚治疗非小细胞肺癌的潜在机制。山奈酚的靶点从公共数据库(PharmMapper、Swiss target prediction)中获取,非小细胞肺癌的靶点从疾病数据库(Genecards和TTD)中获取。同时,我们结合GEO数据库收集基因芯片GSE32863和GSE75037以获得差异基因。通过绘制韦恩图,我们得到了山奈酚与非小细胞肺癌的交集靶点。通过富集分析,PI3K/AKT被确定为可能的关键信号通路。通过拓扑分析和分子对接选择PIK3R1、AKT1、EGFR和IGF1R作为关键靶点,并通过分析关键靶点的基因和蛋白表达对这四个关键基因进行进一步验证。这些发现为山奈酚治疗非小细胞肺癌的进一步研究提供了方向。