悪性黒色腫におけるForkhead box M1(FoxM1)の発現と、FoxM1阻害による抗腫瘍効果について
|概要||Aims:Forkhead box M1 (FoxM1) is a transcription factor that regulates cell‐cycle progression and tumour progression, but limited information is available regarding its clinical significance in melanom...a. The aim of this study was to investigate the potency of FoxM1 as a therapeutic target in melanoma.
Methods and results: We investigated 60 melanoma clinical samples and a melanoma WM266‐4 cell line using immunohistochemical staining and molecular biological approaches. Patients with a FoxM1‐overexpressing melanoma had significantly shorter survival [both for melanoma‐specific survival (MSS) and disease‐free survival (DFS)] than the other patients (P < 0.001, respectively). The FoxM1 overexpression was also an adverse prognostic factor for both MSS and DFS on the Cox multivariate analyses [hazard ratio (HR): 3.96, 95% confidence interval (CI): 1.12–14.27, P = 0.032; HR: 3.21, 95% CI: 1.08–9.67, P = 0.037, respectively). FoxM1 inhibition using siRNA and an inhibitor (thiostrepton) each suppressed the cell proliferation of the melanoma cell line. Furthermore, FoxM1 inhibition improved chemosensitivity to dacarbazine, whereas it reduced cell migration and invasion. These results suggest that FoxM1 plays important roles in tumour progression and the chemoresistance of melanoma.
Conclusion: We have shown the prognostic impact of FoxM1 on melanoma patients. FoxM1 inhibition may be a potential therapeutic option for advanced melanoma.続きを見る