title: Antibiotic drug tigecycline inhibits melanoma progression and metastasis in a p21CIP1/Waf1-dependent manner.
abstract: Antibiotics are common drugs 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.
authors.affiliation: Department of Dermatology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000, P.R. China.|State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, P.R. China.
authors.forename: Huanrong
authors.initials: H
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Tan
authors.affiliation: Department of Dermatology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000, P.R. China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000, P.R. China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, P.R. China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Dermatology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000, P.R. China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, P.R. China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Cui
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019927:Cyclin E / Q000096:biosynthesis; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000517:prevention & control; D015513:Oncogene Proteins / Q000096:biosynthesis; D012878:Skin Neoplasms; D000078304:Tigecycline; D023041:Xenograft Model Antitumor Assays; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000970:Antineoplastic Agents; C475820:CCNE1 protein, human; C493956:CDKN1A protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015513:Oncogene Proteins; D000078304:Tigecycline; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D008911:Minocycline
keywords: cell growth and proliferation; cell migration and invasion; melanoma; p21CIP1/Waf1; tigecycline