Ma Xiaokun, Zhang Miao, Xia Wei, Song Yanan
Department of Nuclear Medicine, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Central Laboratory, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Fitoterapia. 2023 Oct;170:105665. doi: 10.1016/j.fitote.2023.105665. Epub 2023 Sep 4.
Effective therapies for anaplastic thyroid cancer (ATC) are still limited due to its dedifferentiated phenotype and high invasiveness. Xiaoying Sanjie Decoction (XYSJD), a clinically empirical Chinese medicine compound, has shown positive effects for ATC treatment and recovery. However, the pharmacological mechanisms of effective active compound in XYSJD remain unclear. In this study, we aimed at elucidating the antitumor mechanism of the active compound and identifying the kernel molecular mechanisms of XYSJD against ATC. Firstly, the main chemical constituents of XYSJD were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Then we used network pharmacology and ClusterONE algorithm to analyze the possible targets and pathways of the prescription and active compound Saikosaponin A (SSA). Seven core targets, including P2RY12, PDK1, PPP1CC, PPP2CA, TBK1, ITGB1 and ITGB6, which may be involved in the anti-tumor activity of XYSJD were screened. Finally, using cell biology, molecular biology and experimental zoology techniques, we investigated the mechanism of active compound SSA in the treatment of ATC. The results of qRT-PCR indicated that these seven nuclear targets might play an important role in SSA, the active compound of XYSJD. The combined data provide preliminary study of the pharmacological mechanisms of SSA in XYSJD. SSA may be a promising potential therapeutic and chemopreventive candidate for ATC.
由于间变性甲状腺癌（ATC）的去分化表型和高侵袭性，其有效的治疗方法仍然有限。消瘿散结汤（XYSJD）是一种临床经验性的中药复方，已显示出对ATC治疗和康复的积极作用。然而，XYSJD中有效活性成分的药理机制仍不清楚。在本研究中，我们旨在阐明活性成分的抗肿瘤机制，并确定XYSJD抗ATC的核心分子机制。首先，通过超高效液相色谱-四极杆飞行时间质谱（UPLC-QTOF-MS）鉴定XYSJD的主要化学成分。然后我们使用网络药理学和ClusterONE算法分析该方剂和活性成分柴胡皂苷A（SSA）的可能靶点和途径。筛选出七个可能参与XYSJD抗肿瘤活性的核心靶点，包括P2RY12、PDK1、PPP1CC、PPP2CA、TBK1、ITGB1和ITGB6。最后，利用细胞生物学、分子生物学和实验动物学技术，我们研究了活性成分SSA治疗ATC的机制。qRT-PCR结果表明，这七个核心靶点可能在XYSJD的活性成分SSA中发挥重要作用。综合数据为SSA在XYSJD中的药理机制提供了初步研究。SSA可能是一种有前途的ATC潜在治疗和化学预防候选药物。
