Fu-Min Shang1, Jing Li2. 1. Department of Dermatology, Shandong Provincial Xintai People's Hospital, Xintai, Shandong, PR China. 2. Department of Dermatology, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, PR China. Electronic address: lijing810222@126.com.
Abstract
INTRODUCTION: Melanoma is the most dangerous skin cancer with high metastasis rate and mortality. Although the emergence of immunotherapy has brought hope for treatment, the mortality rate of melanoma is still increasing year by year. The underlying mechanism of melanoma tumor progression and metastasis is urgently needed to be clarified. Recently chemokines have been found to play an important role in tumor progression in addition to their immunocytochemical chemotaxis. METHODS: In this study, human melanoma cell lines A375 and M14 were treated with SCH-527123, a small molecule antagonist of CXCR1 and CXCR2. The effects of treatment with SCH-527123 on melanoma cell proliferation, migration and invasion were evaluated in vitro by CCK-8, colony formation and transwell assays. Apoptosis was also detected by flow cytometry staining with annexin V and propidium iodide (PI). The molecular mechanisms of antagonist mediated were detected by western blot. RESULTS: The results showed that SCH-527123 inhibited the proliferation, migration and invasion of melanoma cell lines and promoted apoptosis. The expression of CXCR1 and CXCR2 was downregulated after treatment with SCH-527123. PI3K/AKT pathway and downstream signaling were also inhibited at molecular level owing to treated with SCH-527123. CONCLUSION: In conclusion, our study demonstrated that SCH-527123, a small-molecule antagonist for CXCR1 and CXCR2 inhibited cell proliferation, migration and invasion in melanoma via PI3K/AKT pathway.
INTRODUCTION:Melanoma is the most dangerous skin cancer with high metastasis rate and mortality. Although the emergence of immunotherapy has brought hope for treatment, the mortality rate of melanoma is still increasing year by year. The underlying mechanism of melanoma tumor progression and metastasis is urgently needed to be clarified. Recently chemokines have been found to play an important role in tumor progression in addition to their immunocytochemical chemotaxis. METHODS: In this study, humanmelanoma cell lines A375 and M14 were treated with SCH-527123, a small molecule antagonist of CXCR1 and CXCR2. The effects of treatment with SCH-527123 on melanoma cell proliferation, migration and invasion were evaluated in vitro by CCK-8, colony formation and transwell assays. Apoptosis was also detected by flow cytometry staining with annexin V and propidium iodide (PI). The molecular mechanisms of antagonist mediated were detected by western blot. RESULTS: The results showed that SCH-527123 inhibited the proliferation, migration and invasion of melanoma cell lines and promoted apoptosis. The expression of CXCR1 and CXCR2 was downregulated after treatment with SCH-527123. PI3K/AKT pathway and downstream signaling were also inhibited at molecular level owing to treated with SCH-527123. CONCLUSION: In conclusion, our study demonstrated that SCH-527123, a small-molecule antagonist for CXCR1 and CXCR2 inhibited cell proliferation, migration and invasion in melanoma via PI3K/AKT pathway.