title: Therapeutic effects of antibiotic drug tigecycline against cervical squamous cell carcinoma by inhibiting Wnt/β-catenin signaling.
abstract: Aberrant activation of the Wnt/β-catenin signaling pathway is common in human cervical cancers and has great potential therapeutic value. We show that tigecycline, a FDA-approved antibiotic drug, targets cervical squamous cell carcinoma through inhibiting Wnt/β-catenin signaling pathway. Tigecycline is effective in inducing apoptosis, inhibiting proliferation and anchorage-independent colony formation of Hela cells. The inhibitory effects of tigecycline are further enhanced upon combination with paclitaxel, a most commonly used chemotherapeutic drug for cervical cancer. In a cervical xenograft model, tigecycline inhibits tumor growth as a single agent and its combination with paclitaxel significantly inhibits more tumor growth throughout the duration of treatment. We further show that tigecycline decreases level of both cytoplasmic and nuclear β-catenin and suppressed Wnt/β-catenin-mediated transcription through increasing levels of Axin 1 in Hela cells. In addition, stabilization or overexpression of β-catenin using pharmacological and genetic approaches abolished the effects of tigecycline in inhibiting proliferation and inducing apoptosis of Hela cells. Our study suggests that tigecycline is a useful addition to the treatment armamentarium for cervical cancer and targeting Wnt/β-catenin represents a potential therapeutic strategy in cervical cancer.
authors.affiliation: Department of Obstetrics and Gynaecology, JingZhou Hospital Affiliated to Huazhong University of Science and Technology, Jingzhou, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynaecology, JingZhou Hospital Affiliated to Huazhong University of Science and Technology, Jingzhou, PR China.
authors.forename: Shun
authors.initials: S
authors.lastname: Jiao
authors.affiliation: Department of Obstetrics and Gynaecology, RenMin Hospital of Wuhan University, Wuhan, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Clinical Medicine, Medical School of Yangtze University, Jingzhou, PR China.
authors.forename: Hasina
authors.initials: H
authors.lastname: Banu
authors.affiliation: Department of Clinical Medicine, Medical School of Yangtze University, Jingzhou, PR China.
authors.forename: Shreejana
authors.initials: S
authors.lastname: Hamal
authors.affiliation: Department of Obstetrics and Gynaecology, JingZhou Hospital Affiliated to Huazhong University of Science and Technology, Jingzhou, PR China. Electronic address: Dr.XianRong.Wang@hotmail.com.
authors.forename: Xianrong
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D060466:Axin Protein / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017239:Paclitaxel / Q000008:administration & dosage; D000078304:Tigecycline; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C555451:AXIN1 protein, human; D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D060466:Axin Protein; C495270:CTNNB1 protein, human; D051176:beta Catenin; D000078304:Tigecycline; D008911:Minocycline; D017239:Paclitaxel
keywords: Cervical cancer; Drug repurposing; Tigecycline; Wnt/β-catenin signaling