Antibiotic drug tigecycline inhibits melanoma progression and metastasis in a p21CIP1/Waf1-dependent manner
Metrics: PDF 748 views | HTML 1006 views | ?
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
Yaling Liu, e-mail: email@example.com
Hongjuan Cui, e-mail: firstname.lastname@example.org
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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.