Antibiotic drug tigecycline inhibits melanoma progression and metastasis in a p21CIP1/Waf1-dependent manner

Abstract

// Huanrong Hu 1, 2, * , Zhen Dong 2, * , Peng Tan 2 , Yanli Zhang 1 , Lichao Liu 1 , Liqun Yang 2 , Yaling Liu 1 , Hongjuan Cui 2 1 Department of Dermatology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000, P.R. China 2 State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, P.R. China * These authors have contributed equally to this work Correspondence to: Yaling Liu, e-mail: yzling_liu@126.com Hongjuan Cui, e-mail: hcui@swu.edu.cn Keywords: tigecycline, melanoma, p21CIP1/Waf1, cell growth and proliferation, cell migration and invasion Received: August 04, 2015      Accepted: November 16, 2015      Published: November 28, 2015 ABSTRACT Antibiotics are common durgs with low toxicity but high effectiveness. They have been suggested to be drug candidates for cancer therapy in recent years. Here, we tried to investigate the antitumour effect of tigecycline on malignant melanoma. We showed that tigecycline dramatically inhibited cell proliferation and induced cell cycle arrest at G0/G1 phase. At the same time, tigecycline suppressed cell invasion and migration through preventing epithelial-mesenchymal transition (EMT) process. In addition, tigecycline also significantly blocked tumor growth in vivo . Expression of cell cycle-related proteins were investigated and resulted in downregulation of G1/S checkpoint proteins, such as CDK2 and Cyclin E. However, cyclin-dependent kinase inhibitor 1 (CDKN1A, p21 CIP1/Waf1 ) was downregulated after tigecycline treatment, which was not conformed to its conventional function. To explain this, we overexpressed p21 in melanoma cells. We found that p21 overexpression significantly rescued tigecycline-induced cell proliferation inhibition as well as migration and invasion suppression. Taken together, our results revealed that the essential role of p21 in the inhibitory effect of tigecycline on proliferation, migration and invasion of melanoma. Tigecycline might act as a candidate therapeutic drug for treatment of patients suffering from malignant melanoma.