Drug Design, Development and Therapy (Oct 2021)
Triptolide is a Promising Therapeutic Approach in Treating Thyroid Cancer Based on in silico and in vitro Experiment
Abstract
Fang Wang,1,* Shu-Jing An,2,* Yirong Yin,1,* Juan-Juan Li,1 Chun-Hui Sun,3 Jie Lan,1 Wen-Juan Zhao,1 Cheng-Qian Li1 1Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2Department of Oral Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 3Department of Endocrinology, The Third People’s Hospital of Qingdao Affiliated to Qingdao University, Qingdao, 266003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen-Juan Zhao; Cheng-Qian LiDepartment of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, Shandong Province, People’s Republic of ChinaEmail [email protected]; [email protected]: Thyroid cancer is a familiar kind of cancer. Natural products are promising therapeutic approaches in treating thyroid cancer. Triptolide is a diterpenoid epoxide extracted from Tripterygium wilfordii. The mechanism of triptolide in the treatment of thyroid cancer has not been investigated clearly.Methods: We evaluated triptolide targets and thyroid cancer targets with related databases. The protein–protein interaction (PPI) networks of the triptolide targets and thyroid cancer targets were constructed with Cytoscape software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the core PPI network were obtained. Molecular docking analysis was used to evaluated the binding of triptolide with core targets. Furthermore, apoptosis assays, real-time polymerase chain reaction (RT-PCR) and Western blotting were used to evaluate the anticancer functions of triptolide.Results: Triptolide had 34 targets, and thyroid cancer had 210 targets. The core PPI network of merged PPI networks had 164 nodes and 4513 edges. GO and KEGG enrichment analyses showed that triptolide were related to the cell cycle, apoptosis, and inflammatory signaling pathways. Molecular docking analysis showed that triptolide directly reacted with four core targets: cyclin-dependent kinase inhibitor 1A (CDKN1A), c-JUN, RELA, and tumor protein p53 (TP53). CB-Dock analysis indicated that triptolide could stably bind to core targets. Triptolide inhibited the growth but induced apoptosis of thyroid cancer cells. Triptolide increased the mRNA expression of CDKN1A and TP53 but reduced the mRNA expression of c-JUN and RELA, as shown by RT-PCR. Triptolide increased the protein levels of CDKN1A and phospho-p53 but reduced those of phospho-c-JUN and phospho-NF-κB p65, as shown by Western blotting.Discussion: We considered that triptolide could treat thyroid cancer by inhibiting cell proliferation, inducing apoptosis and inhibiting inflammatory pathways such as the NF-κB and MAPK signaling pathways. CDKN1A, c-JUN, RELA, and TP53 were involved in the antithyroid cancer mechanism of triptolide.Keywords: triptolide, thyroid cancer, molecular docking, apoptosis, inflammation
