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.
Highlights
Malignant melanoma (MM) is a kind of highly aggressive dermatological malignancy with a poor prognosis
Tigecycline inhibited cell growth and proliferation in human melanoma cells To assess the effect of tigecycline in proliferation inhibition, different concentration of tigecycline were treated in human melanoma A375 and MV3 cells
These results demonstrated that tigecycline dramatically inhibited cell growth and proliferation in human melanoma cells
Summary
Malignant melanoma (MM) is a kind of highly aggressive dermatological malignancy with a poor prognosis. The incidence of malignant melanoma is increasing [1]. It is considered that metastasis of melanoma has contributed to the rising morbidity and increasing mortality of skin neoplasms. Even in patients with thin small primary tumors, metastasis of melanoma occurs [3]. Despite tremendous advances have been made in multimodality therapies including surgery, radiation and chemotherapy, the prognosis for malignant metastatic melanoma remains extremely poor [4]. It is time to investigate some novel drugs with high efficiency and minimal toxicity for metastatic melanoma. Identification of effective strategies for the treatment of metastatic melanoma remains an urgent need
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