Papi A, Bartolini G, Ammar K, Guerra F, Ferreri A M, Rocchi P, Orlandi M
Department of Experimental Evolutive Biology, University of Bologna, 40126 Bologna, Italy.
Oncol Rep. 2007 Oct;18(4):1015-21. doi: 10.3892/or.18.4.1015.
Glioblastomas, the most malignant and prevalent brain tumors which remain incurable, are characterized by both extensive proliferation and invasive growth. We previously reported a remarkable antitumoral effect of the retinoid 6-OH-11-O-hydroxyphenantrene (IIF) on neuroblastoma, leukemia and colon carcinoma cells. In this study we examined the effect of IIF on proliferation, apoptosis and cell invasion in the human glioblastoma cell line U87MG, in comparison with all-trans-retinoic acid (RA). Our results showed that both retinoids induced cell growth inhibition and apoptosis in a dose- and time-dependent manner. We also demonstrated that the invasive ability of glioblastoma cells decreased after treatment with IIF or RA. Since cell invasion involves a complex system of tightly regulated proteases, matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of MMPs (TIMPs), we analysed the effect of IIF on MMP and TIMP expression in comparison with RA. Treatment with both retinoids resulted in a marked decrease of MMP2 and MMP9 expression and of lytic activity of MMP2. In addition, exposure to IIF led to enhanced expression of TIMP2. Collectively, our results demonstrated the effectiveness of both IIF and RA in inhibiting proliferation, cell migration, and the invasive potential of glioblastoma U87MG cells. Notably, the anticancer activity of IIF, on the whole, was more pronounced than that of RA. Therefore, these findings, besides providing further evidence that IIF may be a powerful tool in the development of cancer treatments, suggest that IIF may have therapeutic potential against the invasiveness of brain tumors.
胶质母细胞瘤是最恶性且最常见的脑肿瘤，仍然无法治愈，其特征是广泛增殖和侵袭性生长。我们之前报道了类视黄醇6-OH-11-O-羟基菲（IIF）对神经母细胞瘤、白血病和结肠癌细胞具有显著的抗肿瘤作用。在本研究中，我们将IIF与全反式维甲酸（RA）进行比较，研究了IIF对人胶质母细胞瘤细胞系U87MG增殖、凋亡和细胞侵袭的影响。我们的结果表明，两种类视黄醇均以剂量和时间依赖性方式诱导细胞生长抑制和凋亡。我们还证明，用IIF或RA处理后，胶质母细胞瘤细胞的侵袭能力降低。由于细胞侵袭涉及一个由严格调控的蛋白酶、基质金属蛋白酶（MMPs）及其特异性抑制剂——基质金属蛋白酶组织抑制剂（TIMPs）组成的复杂系统，我们分析了IIF与RA相比对MMP和TIMP表达的影响。两种类视黄醇处理均导致MMP2和MMP9表达以及MMP2的裂解活性显著降低。此外，暴露于IIF导致TIMP2表达增强。总体而言，我们的结果证明了IIF和RA在抑制胶质母细胞瘤U87MG细胞增殖、细胞迁移和侵袭潜力方面的有效性。值得注意的是，总体而言，IIF的抗癌活性比RA更显著。因此，这些发现除了进一步证明IIF可能是癌症治疗开发中的有力工具外，还表明IIF可能对脑肿瘤的侵袭性具有治疗潜力。
