Guo Xing, Wang Rui-Sheng, Zhang Zhen-Ling, Zhang Hong-Wei, Wang Sheng-Chao, Zhang Shuai, Wu Ya-Ning, Li Ya-Jing, Yuan Jun
School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.
Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan Province, Zhengzhou, China.
Front Pharmacol. 2024 Oct 23;15:1449498. doi: 10.3389/fphar.2024.1449498. eCollection 2024.
Non-small cell lung cancer (NSCLC) is a prominent lung cancer disease worldwide. Currently, commonly used methods, such as surgery and radiotherapy, have significant side effects. Traditional Chinese medicine (TCM) has become a research hotspot because of its safe and effective characteristics. The branches and leaves of are abundant in antitumor active compounds, and there has been no research conducted as yet regarding its anti-lung cancer molecular mechanism.
The aim of this study is to investigate the antitumor activity of two samples before and after fermentation of , and to research the molecular mechanism of its inhibitory effect on NSCLC.
The chemical composition of pre-fermentation (TM) and post-fermentation qu (TMQ) were investigated using UHPLC-Q-Qrbitrap HRMS and high-performance liquid chromatography (HPLC). The anti-lung cancer activities of TM and TMQ were compared using an A549-induced tumor mouse model. An enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescence were used to determine the of TMQ mechanism of action.
The results indicated that TM and TMQ contained 83 compounds, consisting primarily of flavonoids, organic acids, and taxanes. Both taxanes and flavonoids in TMQ were higher than that in TM. Both TM and TMQ effectively inhibited the tumor growth in non-small cell lung cancer (NSCLC), and the inhibition rate was greater in TMQ (57.24%) than in TM (49.62%). TMQ administration downregulated the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and the glutathione (GSH) level and upregulated interferon-γ (IFN-γ), reactive oxygen species (ROS), and malondialdehyde (MDA) levels in the serum of tumor mice. TMQ treatment also increased the protein expression of Bax, Caspase-3, and Beclin-1 in tumor tissues. In contrast, the bcl-2, PI3K, Ki67, ULK1, and mTOR protein levels were suppressed by TMQ. Protein assay analyses reemphasized the superior antitumor effect of TMQ over TM. These cumulative findings demonstrated that the mechanism of action of TMQ was closely related to the activation of transcriptional misregulation in the cancer pathway that inhibited the cholinergic synaptic, AMPK, and PI3K/Akt/mTOR signaling pathways.
This study demonstrated that fermentation increased the active ingredient contents and antitumor effects of . In addition, post-fermentation TMQ was superior to TM as a herbal medicine for NSCLC treatment.
非小细胞肺癌（NSCLC）是全球一种主要的肺癌疾病。目前，常用方法如手术和放疗有显著副作用。中药因其安全有效的特性已成为研究热点。[植物名称]的枝叶富含抗肿瘤活性化合物，但其抗肺癌分子机制尚无研究。
本研究旨在研究[植物名称]发酵前后两个样品的抗肿瘤活性，并探究其对NSCLC抑制作用的分子机制。
采用超高效液相色谱-四极杆-轨道阱高分辨质谱（UHPLC-Q-Qrbitrap HRMS）和高效液相色谱（HPLC）研究发酵前[植物名称]（TM）和发酵后[植物名称]曲（TMQ）的化学成分。使用A549诱导的肿瘤小鼠模型比较TM和TMQ的抗肺癌活性。采用酶联免疫吸附测定（ELISA）、苏木精-伊红（H&E）染色、免疫组织化学和免疫荧光法确定TMQ的作用机制。
结果表明，TM和TMQ含有83种化合物，主要由黄酮类、有机酸和紫杉烷类组成。TMQ中的紫杉烷类和黄酮类均高于TM。TM和TMQ均能有效抑制非小细胞肺癌（NSCLC）的肿瘤生长，且TMQ的抑制率（57.24%）高于TM（49.62%）。给予TMQ可下调肿瘤小鼠血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和谷胱甘肽（GSH）水平，上调干扰素-γ（IFN-γ）、活性氧（ROS）和丙二醛（MDA）水平。TMQ处理还增加了肿瘤组织中Bax、Caspase-3和Beclin-1的蛋白表达。相反，TMQ抑制了肿瘤组织中bcl-2、PI3K、Ki67、ULK1和mTOR蛋白水平。蛋白质分析再次强调了TMQ比TM具有更强的抗肿瘤作用。这些累积结果表明，TMQ的作用机制与抑制胆碱能突触、AMPK和PI3K/Akt/mTOR信号通路的癌症途径中转录失调的激活密切相关。
本研究表明发酵增加了[植物名称]的活性成分含量和抗肿瘤作用。此外，发酵后的TMQ作为治疗NSCLC的草药优于TM。
