Oncotarget

Research Papers:

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

Huanrong Hu _, Zhen Dong, Peng Tan, Yanli Zhang, Lichao Liu, Liqun Yang, Yaling Liu and Hongjuan Cui

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Oncotarget. 2016; 7:3171-3185. https://doi.org/10.18632/oncotarget.6419

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Abstract

Huanrong Hu1,2,*, Zhen Dong2,*, Peng Tan2, Yanli Zhang1, Lichao Liu1, Liqun Yang2, Yaling Liu1, Hongjuan Cui2

1Department of Dermatology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000, P.R. China

2State 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, p21CIP1/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.


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