Ibrutinib presents antitumor activity in skin cancer and induces autophagy

F.-D. Sun, P.-C. Wang, J. Shang, S.-H. Zou, X. Du

Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, China. zshzqf@163.com

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• Pharmacology

OBJECTIVE: Skin cancer is one of the most common malignancies in dermatology. Patient compliance and prognosis of skin cancer are poor. Ibrutinib, a Bruton’s Tyrosine Kinase (BTK) inhibitor, is a new anticancer drug used to treat many cancers. Therefore, we aimed to explore the role of ibrutinib in the treatment of skin cancer.

MATERIALS AND METHODS: Cell Counting Kit-8 (CCK8) and plate cloning assay were used to detect cell proliferation. Apoptosis was determined by flow cytometry. Western blotting analysis was used to analyze the expression of key proteins that regulated autophagy. Proliferation and apoptosis of skin cancer cells and induction of autophagy induced by ibrutinib were evaluated.

RESULTS: CCK8 plate cloning assays showed that ibrutinib can gradually inhibit the skin cancer cell proliferation as the treatment time and dose increased. Results of flow cytometry showed that apoptosis in skin cancer cells were induced after ibrutinib treatment. Western blot showed that autophagy in skin cancer cells was found induced by ibrutinib and also related to the time and concentration of ibrutinib treatment. Combination treatment of ibrutinib and 3MA for skin cancer cells can significantly increase apoptosis.

CONCLUSIONS: Ibrutinib has anti-tumor activity in skin cancer and can induce autophagy. Binding to autophagy inhibitors can promote ibrutinib’s anti-skin cancer activity. Our experimental results provided new ideas for developing skin cancer drugs.

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