{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:58:15Z","timestamp":1790704695335,"version":"4.1.0"},"reference-count":28,"publisher":"IMR Press","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Social Science and Technology Research Major Project of Zhongshan","award":["2021B3011"],"award-info":[{"award-number":["2021B3011"]}]},{"name":"first batch of social welfare and basic research projects of Zhongshan City in 2023 project","award":["2023B1013"],"award-info":[{"award-number":["2023B1013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmazie"],"abstract":"<jats:p>Background: Thyroid cancer (THCA) has recently become one of the most common endocrine malignancies worldwide. Dihydroartemisinin (DHA) exhibits well-documented antitumor activity, but its therapeutic potential in THCA remains largely unclear. Methods: The relative mRNA and protein expression levels of the apoptosis-related markers Bax, Bcl-2, and Caspase-3 in the human THCA cell line TPC-1 were evaluated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. Potential active targets of DHA were obtained from the TCMSP, SwissTargetPrediction and SuperPred databases. The THCA-related targets were collected from TCGA, DisGeNET and GeneCards. Protein\u2013protein interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict key targets and pathways of DHA against THCA. Results: DHA treatment significantly modulated the expression of apoptosis-related markers, including upregulation of Bax and Caspase-3 and downregulation of Bcl-2, suggesting that DHA may promote apoptosis in TPC-1 cells. A total of 230 potential targets were identified from the overlap between DHA- and THCA-related targets. Indeed, STAT3, PIK3R1, PIK3CA, PIK3CD, MAPK1, MAPK3, EGFR, HSP90AA1, ESR1, PTPN11 were identified as the top 10 hub genes. In total, 2214 biological processes, 118 cellular components, and 220 molecular functions were enriched. KEGG analysis indicated that DHA may suppress THCA primarily via the chemical carcinogenesis-receptor activation pathway. Conclusion: These findings suggest that DHA is a promising candidate for THCA treatment and warrant further investigation, including direct apoptosis assays and in vivo validation.<\/jats:p>","DOI":"10.31083\/pharmazie51720","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:05:53Z","timestamp":1790701553000},"source":"Crossref","is-referenced-by-count":0,"title":["The Potential Mechanism of Dihydroartemisinin in the Treatment of Thyroid Cancer Through Network Pharmacological Analysis"],"prefix":"10.31083","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3534-9142","authenticated-orcid":true,"given":"Xiaozhang","family":"Xie","sequence":"first","affiliation":[{"name":"Department of the Second General Surgery, Zhongshan City People\u2019s Hospital, 528403 Zhongshan, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9522-2203","authenticated-orcid":true,"given":"Jianhang","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of the Second General Surgery, Zhongshan City People\u2019s Hospital, 528403 Zhongshan, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4974-8986","authenticated-orcid":true,"given":"Jianwei","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of the Second General Surgery, Zhongshan City People\u2019s Hospital, 528403 Zhongshan, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3576-7198","authenticated-orcid":true,"given":"Bingxing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of the Second General Surgery, Zhongshan City People\u2019s Hospital, 528403 Zhongshan, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0286-1135","authenticated-orcid":true,"given":"Linkun","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of the Second General Surgery, Zhongshan City People\u2019s Hospital, 528403 Zhongshan, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6284-1662","authenticated-orcid":true,"given":"Liqing","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of the Second General Surgery, Zhongshan City People\u2019s Hospital, 528403 Zhongshan, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3736-3662","authenticated-orcid":true,"given":"Jingjing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Zhongshan City People\u2019s Hospital, 528403 Zhongshan, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Deng Y, Li H, Wang M, Li N, Tian T, Wu Y, et al. Global Burden of Thyroid Cancer From 1990 to 2017. JAMA Network Open. 2020; 3: e208759.","DOI":"10.1001\/jamanetworkopen.2020.8759"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA: a Cancer Journal for Clinicians. 2022; 72: 7\u201333.","DOI":"10.3322\/caac.21708"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England). 2019; 394: 1145\u20131158.","DOI":"10.1016\/S0140-6736(19)30427-1"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Romei C, Tacito A, Molinaro E, Piaggi P, Cappagli V, Pieruzzi L, et al. Clinical, pathological and genetic features of anaplastic and poorly differentiated thyroid cancer: A single institute experience. Oncology Letters. 2018; 15: 9174\u20139182.","DOI":"10.3892\/ol.2018.8470"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid: Official Journal of the American Thyroid Association. 2016; 26: 1\u2013133.","DOI":"10.1089\/thy.2015.0020"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Olatunde OZ, Yong J, Lu C. An Overview of Dihydroartemisinin as a Promising Lead Compound for Development of Anticancer Agents. Mini Reviews in Medicinal Chemistry. 2023; 23: 265\u2013289.","DOI":"10.2174\/1389557522666220425124923"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Hu R, Shi Z, Yang J, Ren Y, Li X. Anti-Ferroptosis: A Promising Therapeutic Method for Thyroid Cancer. Frontiers in Bioscience (Landmark Edition). 2024; 29: 77.","DOI":"10.31083\/j.fbl2902077"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Bai B, Wu F, Ying K, Xu Y, Shan L, Lv Y, et al. Therapeutic effects of dihydroartemisinin in multiple stages of colitis-associated colorectal cancer. Theranostics. 2021; 11: 6225\u20136239.","DOI":"10.7150\/thno.55939"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Guo K, Cao YY, Qian LC, Daniels MJ, Tian Y, Li Y, et al. Dihydroartemisinin induces ferroptosis in pancreatic cancer cells by the regulation of survival prediction-related genes. Traditional Medicine Research. 2023; 8: 67.","DOI":"10.53388\/TMR20230618001"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Yan Y, Yang X, Han N, Liu Y, Liang Q, Li LG, et al. Metal-organic framework-encapsulated dihydroartemisinin nanoparticles induces apoptotic cell death in ovarian cancer by blocking ROMO1-mediated ROS production. Journal of Nanobiotechnology. 2023; 21: 204.","DOI":"10.1186\/s12951-023-01959-3"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Peng Y, Zheng Y, Qiu J, Liu J, Zou J, Liu C, et al. Dihydroartemisinin Enhances the Effects of Oxaliplatin by Activating PDCD5\/ARAF mediated Signal Transduction in Colon Cancer. 2023.  (preprint)","DOI":"10.21203\/rs.3.rs-3353635\/v1"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Wu GS, Lu JJ, Guo JJ, Huang MQ, Gan L, Chen XP, et al. Synergistic anti-cancer activity of the combination of dihydroartemisinin and doxorubicin in breast cancer cells. Pharmacological Reports: PR. 2013; 65: 453\u2013459.","DOI":"10.1016\/s1734-1140(13)71021-1"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Jin M, Shi L, Wang L, Zhang D, Li Y. Dihydroartemisinin enhances the anti-tumour effect of photodynamic therapy by targeting PKM2-mediated glycolysis in oesophageal cancer cell. Journal of Enzyme Inhibition and Medicinal Chemistry. 2024; 39: 2296695.","DOI":"10.1080\/14756366.2023.2296695"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Li R, Zhang X, Ge Y, Zhao Z, Feng L, Li X. Dihydroartemisinin Inhibits Epithelial-Mesenchymal Transition Progression in Medullary Thyroid Carcinoma Through the Hippo Signaling Pathway Regulated by Interleukin-6. Cancer Biotherapy & Radiopharmaceuticals. 2025; 40: 139\u2013150.","DOI":"10.1089\/cbr.2023.0197"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Noor F, Asif M, Ashfaq UA, Qasim M, Tahir Ul Qamar M. Machine learning for synergistic network pharmacology: a comprehensive overview. Briefings in Bioinformatics. 2023; 24: bbad120.","DOI":"10.1093\/bib\/bbad120"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Holm TM, Yeo S, Turner KM, Guan JL. Targeting Autophagy in Thyroid Cancer: EMT, Apoptosis, and Cancer Stem Cells. Frontiers in Cell and Developmental Biology. 2022; 10: 821855.","DOI":"10.3389\/fcell.2022.821855"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Tang M, Luo W, Zhou Y, Zhang Z, Jiang Z. Anoikis-related gene CDKN2A predicts prognosis and immune response and mediates proliferation and migration in thyroid carcinoma. Translational Oncology. 2024; 40: 101873.","DOI":"10.1016\/j.tranon.2023.101873"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Phikulsod P, Kariya R, Panaampon J, Okada S. Dihydroartemisinin Induced Apoptosis and Synergized With Chemotherapy in Pleural Effusion Lymphoma Cells. Anticancer Research. 2023; 43: 1139\u20131148.","DOI":"10.21873\/anticanres.16259"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Abbasi Y, Pooladi M, Nazmabadi R, Amri J, Abbasi H, Karami H. Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell Lines. Cell Journal. 2024; 26: 121\u2013129.","DOI":"10.22074\/cellj.2024.2016937.1459"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Luo L, Zhou B. Anticancer Potential of Artemisinin Derivative-Dihydroartemisinin. Highlights in Science, Engineering and Technology. 2023; 33: 236\u2013243.","DOI":"10.54097\/hset.v33i.5327"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Yu R, Jin G, Fujimoto M. Dihydroartemisinin: A potential drug for the treatment of malignancies and inflammatory diseases. Frontiers in Oncology. 2021; 11: 722331.","DOI":"10.3389\/fonc.2021.722331"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Sosonkina N, Starenki D, Park JI. The Role of STAT3 in Thyroid Cancer. Cancers. 2014; 6: 526\u2013544.","DOI":"10.3390\/cancers6010526"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Arafeh R, Samuels Y. PIK3CA in cancer: The past 30 years. Seminars in Cancer Biology. 2019; 59: 36\u201349.","DOI":"10.1016\/j.semcancer.2019.02.002"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Chen DW, Lang BHH, McLeod DSA, Newbold K, Haymart MR. Thyroid cancer. Lancet. 2023; 401: 1531\u20131544.","DOI":"10.1016\/S0140-6736(23)00020-X"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Glaviano A, Foo ASC, Lam HY, Yap KCH, Jacot W, Jones RH, et al. PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer. Molecular Cancer. 2023; 22: 138.","DOI":"10.1186\/s12943-023-01827-6"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Xue C, Yao Q, Gu X, Shi Q, Yuan X, Chu Q, et al. Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer. Signal Transduction and Targeted Therapy. 2023; 8: 204.","DOI":"10.1038\/s41392-023-01468-7"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Su Z, Song J, Wang Z, Zhou L, Xia Y, Yu S, et al. Tumor promoter TPA activates Wnt\/\u03b2-catenin signaling in a casein kinase 1-dependent manner. Proceedings of the National Academy of Sciences of the United States of America. 2018; 115: E7522\u2013E7531.","DOI":"10.1073\/pnas.1802422115"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Cho WCS. Targeting the signaling pathways in cancer therapy. 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