Title:Network Pharmacological Analysis and Experimental Validation of the
Effects of Silybin on Proliferation, Migration, and Immunotherapy of
Papillary Thyroid Cancer
Volume: 24
Issue: 6
Author(s): Wenjun Xie*, Huashui Li, Qiang Lin and Naizhuo Ke
Affiliation:
- Department of General Surgery, Shengli Clinical Medical College of Fujian Medical University, General Surgery Clinical
Key Speciality of Fujian Provincial Hospital, Fuzhou, Fujian, 350001, People’s Republic of China
- Fujian Medical University,
Fujian, 350001, People’s Republic of China
Keywords:
Silybin, papillary thyroid cancer, network pharmacology, FN1/AKT, EMT process, immunosuppression.
Abstract:
Aim: The study aimed to use network pharmacology research and in vitro experiments
to investigate the material basis and molecular mechanisms of silybin in the treatment of papillary
thyroid carcinoma.
Background: Papillary thyroid cancer (PTC) has a decent prognosis; however, recurrence and metastasis
are the leading causes of death in patients with PTC. A key research focus in thyroid cancer
treatment is the inhibition of PTC proliferation, invasion, and migration. Silybin, the major active
element in the traditional Chinese herb silymarin, has been used to treat a range of diseases, including
cancer, but no study has been undertaken to determine whether it can help prevent PTC.
Objective: In this study, we attempted to determine through network pharmacology and in vitro
experiments if silybin inhibits the development of papillary thyroid cancer by inhibiting cell cycle
and invasive migration.
Methods: To predict the probable targets and underlying mechanisms of silybin against PTC, a
network pharmacology research was performed. In vitro experiments were conducted to further
evaluate silybin's anti-cancer properties and priority targets against PTC.
Results: The datasets revealed a total of 489 silybin targets acting on PTC, and functional enrichment
analysis suggested that the target genes were enriched in functions and pathways related to
PTC development, invasion, migration, and immunotherapy. By constructing these target PPI networks,
the seven hub genes, fibronectin 1 (FN1), tissue inhibitor of metalloproteinases 1 (TIMP1),
N-cadherin (CDH2), collagen type III alpha 1 chain (COL3A1), cyclin D1 (CCND1), AP-1 transcription
factor subunit (JUN), and hepatocyte growth factor receptor (MET) were found. These
hub genes were determined to be highly linked to a worse clinicopathological form, a higher risk of
metastatic recurrence, and a worse prognosis of PTC. The common immunological checkpoint
gene expression levels were positively correlated with the expression levels of the hub genes. Silybin
decreased the proliferative and metastatic capacity of PTC cells, according to in vitro investigations.
When PTC was treated with silybin, the FN1/AKT signaling pathway was blocked,
CCND1 expression was reduced, and CDH2, Vimentin, Snail, Slug and PD-L1 expressions were
dramatically reduced, while E-cadherin expression was significantly elevated.
Conclusion: These findings provide preliminary evidence that silybin inhibits PTC cell proliferation,
metastasis, and invasion by altering the FN1/AKT signaling pathway and inhibiting the EMT
process. Silybin can reverse immunosuppression in papillary thyroid cancer by affecting immunological
checkpoint gene expression levels. These studies provide a theoretical and experimental
scientific basis for the potential anticancer effects of silybin on PTC.
