RRC ID 89804
著者 Hattori T, Fujii M, Ueda T, Ishikawa A, Mine Y, Xu B, Suehiro T, Hattori M, Tahara H, Sato Y, Chikuie N, Taruya T, Hamamoto T, Ishino T, Takeno S.
タイトル Exploration of Therapeutic Targets Using CDK4 Inhibitors for Head and Neck Mucosal Melanoma.
ジャーナル Otolaryngol Head Neck Surg
Abstract OBJECTIVE:Mucosal melanoma (MM) is an extremely aggressive malignant tumor in the head and neck region associated with a poor prognosis. In the present study, we conducted cell proliferation assay and western blotting using cell lines derived from MM and the immunohistochemical analysis of pathological MM tissues to identify novel therapeutic targets. Herein, we report on the potential of cyclin-dependent kinase 4 (CDK4) inhibitors as molecular targeted therapies for MM.
STUDY DESIGN:Retrospective cohort study and laboratory analysis.
SETTING:A tertiary referral center.
METHODS:MTT assay and western blotting were performed on the HMV-II (RCB0777) and GAK (JCRB0180) cell lines, treated with the CDK4 inhibitors abemaciclib (LY2835219) and palbociclib (PD-0332991). This retrospective cohort study included patients with head and neck MM; immunohistochemistry was performed on clinical specimens.
RESULTS:Abemaciclib and palbociclib showed concentration-dependent cytostatic effects on HMV-II and GAK cells at 72 hours in the MTT assay. In western blotting, they exhibited concentration-dependent inhibitory effects on phosphorylated RB1 in HMV-II and GAK cells at 24 hours. Of 23 patients, 18 (78.3%) had positive results on CDK4 immunostaining. No clinicopathologic factors were significantly associated with CDK4 status.
CONCLUSION:Abemaciclib and palbociclib may suppress MM cell proliferation. The CDK4 signaling pathway is a potential target for molecular-targeted therapies in MM.
巻・号 174(3)
ページ 784-791
公開日 2026-3-1
DOI 10.1002/ohn.70137
PMID 41568999
PMC PMC12948400
MeSH Aged Aminopyridines* / pharmacology Aminopyridines* / therapeutic use Benzimidazoles* / pharmacology Benzimidazoles* / therapeutic use Blotting, Western Cell Line, Tumor Cell Proliferation / drug effects Cyclin-Dependent Kinase 4* / antagonists & inhibitors Female Head and Neck Neoplasms* / drug therapy Head and Neck Neoplasms* / pathology Humans Immunohistochemistry Male Melanoma* / drug therapy Melanoma* / pathology Middle Aged Molecular Targeted Therapy Mucous Membrane / pathology Piperazines* / pharmacology Piperazines* / therapeutic use Pyridines* / pharmacology Pyridines* / therapeutic use Retrospective Studies
リソース情報
ヒト・動物細胞 HMV-II(RCB0777)