title: Tumor growth suppression by inhibiting both autophagy and STAT3 signaling in HNSCC.
abstract: Autophagy is considered as a double-edged sword. It can prolong the survival of cancer cells and enhance its resistance to apoptosis, and paradoxically, defective autophagy has been linked to increased tumorigenesis, but the mechanism behind this phenomenon is unclear. In this study, we demonstrated that decreased phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) was correlated with increased autophagy through the Akt/mTOR and Erk signaling pathways in human head and neck squamous cell carcinoma (HNSCC). We also showed that blockage of STAT3 by NSC74859 could markedly induce apoptotic cell death and autophagy. Meanwhile, increased autophagy inhibited apoptosis. The pharmacological or genetic inhibition of autophagy and STAT3 further sensitized HNSCC cells to apoptosis. Furthermore, evidence from xenograft model proved that suppressed STAT3 activity combined with inhibition of autophagy promoted tumor regression better than either treatment alone. Taken together, this present study demonstrated that autophagy alleviates apoptotic cell death in HNSCC, and combination of inhibition of STAT3 by NSC74859 and autophagy might be a promising new therapeutic strategy for HNSCC.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Teng-Fei
authors.initials: TF
authors.lastname: Fan
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Bu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Wang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Si-Rui
authors.initials: SR
authors.lastname: Ma
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Liu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Deng
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Mao
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Guang-Tao
authors.initials: GT
authors.lastname: Yu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Cong-Fa
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.|Department of Oral and Maxillofacial-Head and Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.|Department of Oral and Maxillofacial-Head and Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Sun
mesh_terms: D000636:Aminosalicylic Acids / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D001557:Benzenesulfonates / Q000494:pharmacology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016000:Cluster Analysis; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D046888:Tissue Array Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000636:Aminosalicylic Acids; D001557:Benzenesulfonates; C520337:NSC 74859; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: STAT3; apoptosis; autophagy; head and neck cancer