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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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Li H,Jiao S,Li X,Banu H,Hamal S,Wang X

doi

10.1016/j.bbrc.2015.09.140

subject

Has Abstract

pub_date

2015-11-06 00:00:00

pages

14-20

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(15)30656-2

journal_volume

467

pub_type

杂志文章

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