Yamazoe Yuzuru, Tsubaki Masanobu, Matsuoka Hiroshi, Satou Takao, Itoh Tatsuki, Kusunoki Takashi, Kidera Yasuhiro, Tanimori Yoshihiro, Shoji Kaori, Nakamura Haruyuki, Ogaki Mitsuhiko, Nishiura Saori, Nishida Shozo
Division of Pharmacotherapy, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan.
Cell Biol Int. 2009 Oct;33(10):1087-94. doi: 10.1016/j.cellbi.2009.06.027. Epub 2009 Jul 10.
NF-kappaB acts as a signal transducer during tumor progression, cell invasion, and metastasis. Dimethylfumarate (DMF) is reported to inhibit tumor necrosis factor-alpha-induced nuclear entry of NF-kappaB/p65. However, only a few reports suggest that DMF inhibits tumor metastasis; also the molecular mechanisms underlying the inhibition of metastasis are poorly understood. We investigated the inhibition of tumor invasion and metastasis by DMF in a melanoma cell line, B16BL6. DMF inhibited B16BL6 cell invasion and metastasis by suppressing the expression and activities of MMPs. DMF also inhibited the nuclear entry of NF-kappaB/p65, thus inhibiting B16BL6 cell invasion and metastasis. These results suggest that DMF is potentially useful as an anti-metastatic agent for the treatment of malignant melanoma.
核因子-κB在肿瘤进展、细胞侵袭和转移过程中充当信号转导分子。据报道，富马酸二甲酯（DMF）可抑制肿瘤坏死因子-α诱导的核因子-κB/p65进入细胞核。然而，仅有少数报道表明DMF可抑制肿瘤转移；而且，抑制转移的分子机制仍知之甚少。我们研究了DMF对黑色素瘤细胞系B16BL6肿瘤侵袭和转移的抑制作用。DMF通过抑制基质金属蛋白酶（MMPs）的表达和活性来抑制B16BL6细胞的侵袭和转移。DMF还抑制核因子-κB/p65进入细胞核，从而抑制B16BL6细胞的侵袭和转移。这些结果表明，DMF作为一种抗转移药物，在恶性黑色素瘤治疗中具有潜在应用价值。
