Zhou Xiangnan, Hu Xiuhua, Zhang Zhiying, Lin Shicheng, Lin Ximing, Zhou Tian, Bai Yanping, Hu Kaiwen
Department of Dermatology, China-Japan Friendship Hospital, National Center for Integrated Traditional Chinese and Western Medicine, Beijing, 100029, People's Republic of China.
Department of Oncology, East Hospital, Beijing University of Chinese Medicine, Beijing, 100078, People's Republic of China.
Cancer Manag Res. 2025 Jul 24;17:1487-1501. doi: 10.2147/CMAR.S510010. eCollection 2025.
Xingxiao Pill (XXP), a typical traditional Chinese medicine (TCM) prescription drug used to treat NSCLC in clinic. However, the mechanism underlying its regulatory effects remains unclear. This study aimed to evaluate the potential efficacy of XXP in treating NSCLC and to investigate how XXP regulates fatty acid biosynthesis in NSCLC.
A lung carcinoma mouse model was created by transplanting Lewis lung carcinoma (LLC) cells into male C57BL/6 mice. Lung cancer cell models using LLC and A549 cells were also constructed. XXP's therapeutic efficacy on NSCLC was assessed via oral gavage. Bioinformatics analysis and transcriptome sequencing identified XXP's potential targets and mechanisms. These findings were verified by in vitro cell assays, Western blotting, immunofluorescence staining, and Oil Red O staining.
XXP inhibited lung tumor growth, suppressed cell proliferation and impeded cell migration. Additionally, it influenced the processes of apoptosis and cell cycle in both A549 and LLC cells. Bioinformatics analysis suggested that regulation of fatty acid biosynthesis and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were crucial mechanisms underlying the antitumor effects of XXP in lung cancer. XXP reduced the levels of the fatty acid biosynthesis products, such as total cholesterol (TC), triglycerides (TG), lipids, and free fatty acids in A549 cells, and downregulated the expression of sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN). Furthermore, XXP decreased the expression level of PI3K, AKT, mTOR, phospho-PI3K, and phospho-AKT.
XXP exerts its inhibitory effect on lung cancer tumor growth by controlling the biosynthesis of fatty acids and the PI3K/AKT/mTOR signaling pathway. The research suggests that targeting this metabolic pathway could be a viable strategy for cancer therapy and emphasizes the value of TCM in providing a rich source of innovative pharmaceuticals for cancer treatment.
杏香片（XXP）是一种临床上用于治疗非小细胞肺癌（NSCLC）的典型中药处方药。然而，其调节作用的潜在机制尚不清楚。本研究旨在评估XXP治疗NSCLC的潜在疗效，并探究XXP如何调节NSCLC中的脂肪酸生物合成。
通过将Lewis肺癌（LLC）细胞移植到雄性C57BL/6小鼠体内建立肺癌小鼠模型。还构建了使用LLC和A549细胞的肺癌细胞模型。通过灌胃评估XXP对NSCLC的治疗效果。生物信息学分析和转录组测序确定了XXP的潜在靶点和机制。这些发现通过体外细胞试验、蛋白质印迹法、免疫荧光染色和油红O染色进行了验证。
XXP抑制肺肿瘤生长，抑制细胞增殖并阻碍细胞迁移。此外，它影响了A549和LLC细胞中的凋亡和细胞周期进程。生物信息学分析表明，脂肪酸生物合成的调节和磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素哺乳动物靶蛋白（mTOR）信号通路是XXP在肺癌中抗肿瘤作用的关键机制。XXP降低了A549细胞中脂肪酸生物合成产物的水平，如总胆固醇（TC）、甘油三酯（TG）、脂质和游离脂肪酸，并下调了固醇调节元件结合蛋白1（SREBP1）和脂肪酸合酶（FASN）的表达。此外，XXP降低了PI3K、AKT、mTOR、磷酸化PI3K和磷酸化AKT的表达水平。
XXP通过控制脂肪酸生物合成和PI3K/AKT/mTOR信号通路对肺癌肿瘤生长发挥抑制作用。该研究表明，靶向这一代谢途径可能是一种可行的癌症治疗策略，并强调了中药在为癌症治疗提供丰富的创新药物来源方面的价值。
