Antitumor mechanism of Saikosaponin A in the Xiaoying Sanjie Decoction for treatment of anaplastic thyroid cancer by network pharmacology analysis and experiments in vitro and in vivo.

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.