title: Dihydroartemisinin as a Putative STAT3 Inhibitor, Suppresses the Growth of Head and Neck Squamous Cell Carcinoma by Targeting Jak2/STAT3 Signaling.
abstract: Developing drugs that can effectively block STAT3 activation may serve as one of the most promising strategy for cancer treatment. Currently, there is no putative STAT3 inhibitor that can be safely and effectively used in clinic. In the present study, we investigated the potential of dihydroartemisinin (DHA) as a putative STAT3 inhibitor and its antitumor activities in head and neck squamous cell carcinoma (HNSCC). The inhibitory effects of DHA on STAT3 activation along with its underlying mechanisms were studied in HNSCC cells. The antitumor effects of DHA against HNSCC cells were explored both in vitro and in vivo. An investigation on cooperative effects of DHA with cisplatin in killing HNSCC cells was also implemented. DHA exhibited remarkable and specific inhibitory effects on STAT3 activation via selectively blocking Jak2/STAT3 signaling. Besides, DHA significantly inhibited HNSCC growth both in vitro and in vivo possibly through induction of apoptosis and attenuation of cell migration. DHA also synergized with cisplatin in tumor inhibition in HNSCC cells. Our findings demonstrate that DHA is a putative STAT3 inhibitor that may represent a new and effective drug for cancer treatment and therapeutic sensitization in HNSCC patients.
authors.affiliation: Postgraduate School, The Third Medical Military University, Chongqing, 400038, China.|Department of Otolaryngology Head and Neck Surgery, Bethune International Peace Hospital, Shijiazhuang, 050081, Hebei Province, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Bethune International Peace Hospital, Shijiazhuang, 050081, Hebei Province, China.|Postgraduate School, Medical College of PLA, Beijing, 100700, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Song
authors.affiliation: Postgraduate School, The Third Medical Military University, Chongqing, 400038, China.|Department of Otolaryngology Head and Neck Surgery, Bethune International Peace Hospital, Shijiazhuang, 050081, Hebei Province, China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Bethune International Peace Hospital, Shijiazhuang, 050081, Hebei Province, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Hebei General Hospital, Shijiazhuang, 050051, Hebei Province, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Pi
authors.affiliation: Department of Basic Sciences, Hebei College of Traditional Chinese Medicine, Shijiazhuang, 050061, Hebei Province, China.
authors.forename: Xiuru
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Pathology, Bethune International Peace Hospital, Shijiazhuang, 050081, Hebei, Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Postgraduate School, The Third Medical Military University, Chongqing, 400038, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Lu
authors.affiliation: Postgraduate School, The Third Medical Military University, Chongqing, 400038, China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014945:Wound Healing; D023041:Xenograft Model Antitumor Assays
chemical_list: D037621:Artemisinins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C039060:artenimol; C507924:JAK2 protein, human; D053614:Janus Kinase 2