Eugenio Mateus, Campanati Loraine, Müller Nathalia, Romão Luciana F, de Souza Jorge, Alves-Leon Soniza, de Souza Wanderley, Sant'Anna Celso
Laboratory of Microscopy Applied to Life Science - Lamav, National Institute of Metrology, Quality and Technology - Inmetro, Av. Nossa Senhora das Graças, 50, prédio 27- Xerém, Duque de Caxias, RJ, 25250-020, Brazil.
Post-Graduation Program on Translational Biomedicine - Biotrans, Duque de Caxias, Rio de Janeiro, Brazil.
Cytotechnology. 2018 Dec;70(6):1607-1618. doi: 10.1007/s10616-018-0253-1. Epub 2018 Sep 10.
Glioblastomas (GBM) are aggressive brain tumors with very poor prognosis. While silver nanoparticles represent a potential new strategy for anticancer therapy, the silver/silver chloride nanoparticles (Ag/AgCl-NPs) have microbicidal activity, but had not been tested against tumor cells. Here, we analyzed the effect of biogenically produced Ag/AgCl-NPs (from yeast cultures) on the proliferation of GBM02 glioblastoma cells (and of human astrocytes) by automated, image-based high-content analysis (HCA). We compared the effect of 0.1-5.0 µg mL Ag/AgCl-NPs with that of 9.7-48.5 µg mL temozolomide (TMZ, chemotherapy drug currently used to treat glioblastomas), alone or in combination. At higher concentrations, Ag/AgCl-NPs inhibited GBM02 proliferation more effectively than TMZ (up to 82 and 62% inhibition, respectively), while the opposite occurred at lower concentrations (up to 23 and 53% inhibition, for Ag/AgCl-NPs and TMZ, respectively). The combined treatment (Ag/AgCl-NPs + TMZ) inhibited GBM02 proliferation by 54-83%. Ag/AgCl-NPs had a reduced effect on astrocyte proliferation compared with TMZ, and Ag/AgCl-NPs + TMZ inhibited astrocyte proliferation by 5-42%. The growth rate and population doubling time analyses confirmed that treatment with Ag/AgCl-NPs was more effective against GBM02 cells than TMZ (~ 67-fold), and less aggressive to astrocytes, while Ag/AgCl-NP + TMZ treatment was no more effective against GBM02 cells than Ag/AgCl-NPs monotherapy. Taken together, our data indicate that 2.5 µg mL Ag/AgCl-NPs represents the safest dose tested here, which affects GBM02 proliferation, with limited effect on astrocytes. Our findings show that HCA is a useful approach to evaluate the antiproliferative effect of nanoparticles against tumor cells.
胶质母细胞瘤（GBM）是一种侵袭性很强的脑肿瘤，预后很差。虽然银纳米颗粒代表了一种潜在的抗癌治疗新策略，但银/氯化银纳米颗粒（Ag/AgCl-NPs）具有杀菌活性，但尚未针对肿瘤细胞进行测试。在这里，我们通过基于图像的自动化高内涵分析（HCA），分析了生物合成的Ag/AgCl-NPs（来自酵母培养物）对GBM02胶质母细胞瘤细胞（以及人星形胶质细胞）增殖的影响。我们比较了0.1-5.0 μg/mL Ag/AgCl-NPs与9.7-48.5 μg/mL替莫唑胺（TMZ，目前用于治疗胶质母细胞瘤的化疗药物）单独使用或联合使用的效果。在较高浓度下，Ag/AgCl-NPs比TMZ更有效地抑制GBM02增殖（分别高达82%和62%的抑制率），而在较低浓度下情况相反（Ag/AgCl-NPs和TMZ分别高达23%和53%的抑制率）。联合治疗（Ag/AgCl-NPs + TMZ）抑制GBM02增殖达54%-83%。与TMZ相比，Ag/AgCl-NPs对星形胶质细胞增殖的影响较小，Ag/AgCl-NPs + TMZ抑制星形胶质细胞增殖达5%-42%。生长速率和群体倍增时间分析证实，用Ag/AgCl-NPs治疗对GBM02细胞比TMZ更有效（约67倍），对星形胶质细胞的侵袭性更小，而Ag/AgCl-NP + TMZ治疗对GBM02细胞并不比Ag/AgCl-NPs单药治疗更有效。综上所述，我们的数据表明，2.5 μg/mL Ag/AgCl-NPs是这里测试的最安全剂量，它影响GBM02增殖，对星形胶质细胞的影响有限。我们的研究结果表明，HCA是评估纳米颗粒对肿瘤细胞抗增殖作用的一种有用方法。
