Suppressive effect of calcipotriol on the induction of matrix metalloproteinase (MMP)-9 and MMP-13 in a human squamous cell carcinoma cell line
Suppressive effect of calcipotriol on the induction of matrix metalloproteinase (MMP)-9 and MMP-13 in a human squamous cell carcinoma cell line
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DOI：
10.1111/j.1365-2230.2012.04381.x
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发表时间：
2012-12-01
影响因子：
4.1
通讯作者：
Ohtsuki, M.
中科院分区：
文献类型：
--
作者：
Meephansan, J.;Komine, M.;Ohtsuki, M.
背景维生素D3是细胞生长、分化和死亡、肿瘤侵袭和血管生成的有效调节剂。肿瘤细胞产生的基质金属蛋白酶（MMP）-9和MMP-13可促进肿瘤的生长、侵袭和转移。瞄准目的：研究钙泊三醇对人鳞状细胞癌（SCC）细胞株（DJM细胞）MMP-9和MMP-13表达的抑制作用，探讨钙泊三醇对肿瘤坏死因子（TNF）-α诱导的DJM细胞MMP-9和MMP-13表达的调节机制。方法. ELISA法检测MMP-9和MMP-13的蛋白表达，实时荧光定量PCR法检测MMP-13的mRNA表达。使用信号传导分子的几种抑制剂和蛋白质印迹分析评估信号传导级联的激活。结果TNF-α处理后MMP-9和MMP-13的表达明显增加。钙泊三醇可显著抑制MMP-9和MMP-13 mRNA和蛋白的表达，且呈剂量依赖性。由TNF-α诱导的MMP-9被细胞外信号调节激酶（ERK）抑制剂抑制，但不被p38抑制剂抑制，而MMP-13的诱导被p38抑制剂抑制，但不被ERK抑制剂抑制。钙泊三醇抑制ERK和p38的磷酸化，如蛋白质印迹所示。结论钙泊三醇通过分别抑制ERK和p38的磷酸化来减少MMP-9和MMP-13的产生。
Background. Vitamin D3 is a potent regulator of cell growth, differentiation and death, tumour invasion, and angiogenesis. Production of matrix metalloproteinase (MMP)-9 and MMP-13 by tumour cells may promote tumour growth, invasion and metastasis. Aim. To investigate whether calcipotriol could suppress the expression of MMP-9 and MMP-13 in a human squamous cell carcinoma (SCC) cell line (DJM cells), and to examine the mechanism of modulation of MMP-9 and MMP-13 by calcipotriol in DJM cells treated with tumour necrosis factor (TNF)-a. Methods. Protein and mRNA levels of MMP-9 and MMP-13 were examined by ELISA and real-time PCR, respectively. Activation of signalling cascades was assessed using several inhibitors of signalling molecules and western blot analysis. Results. Production of MMP-9 and MMP-13 markedly increased when the cells were treated with TNF-a. Calcipotriol suppressed the production of MMP-9 and MMP-13 mRNA and proteins significantly, in a dose-dependent manner. Induction of MMP-9 by TNF-a was suppressed by an extracellular signal-regulated kinase (ERK) inhibitor but not by a p38 inhibitor, whereas induction of MMP-13 was inhibited by a p38 inhibitor but not by an ERK inhibitor. Calcipotriol inhibited the phosphorylation of both ERK and p38, as shown by western blotting. Conclusion. Calcipotriol reduces MMP-9 and MMP-13 production through inhibiting the phosphorylation of ERK and p38, respectively.