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源自灰黄青霉的氧化锌纳米颗粒通过调节NF-κB相关信号通路减轻DMBA/TPA诱导的小鼠皮肤癌发生。

Zinc oxide nanoparticles derived from Penicillium griseofulvum mitigate DMBA/TPA-promoted mice skin carcinogenesis by modulating NF-ĸB associated signalling.

作者信息

Li Zhongxing, Wu Fenglian, Zhang Qingfu

机构信息

Center of Burn and Wound Repair, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.

Department of Plastic and Aesthetic Surgery, The First Hospital of Qin Huangdao, Qinhuangdao, 066000, Hebei, China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan;398(1):891-902. doi: 10.1007/s00210-024-03311-4. Epub 2024 Jul 30.

DOI:10.1007/s00210-024-03311-4
PMID:39080011
Abstract

This study investigates the synthesis of zinc oxide nanoparticles using Penicillium griseofulvum (ZnONPs-PG) and their potential role in preventing DMBA/TPA-induced skin cancer. The synthesis process involved using a 1-mM zinc acetate dihydrate as a precursor in P. griseofulvum. Various analytical techniques, including FTIR spectroscopy, UV-Vis, TEM, XRD, and DLS, were utilized to characterize the ZnONPs. The efficacy of ZnONPs-PG was then evaluated in a DMBA/TPA-induced skin cancer model. Mice were treated topically with DMBA/TPA in acetone (200 μL) over 2 weeks, with treatments continuing for 20 weeks. Results showed 100% tumor occurrence, histological changes, elevated lipid peroxidation (LPO) levels, and decreased antioxidant levels in DMBA/TPA-treated mice. However, topical application of ZnONPs magnificently reverted the tumor occurrence, histological changes, elevated malanoldehyde and hydrogen peroxide levels; decreased antioxidant levels in DMBA/TPA-treated mice. ZnONPs-PG treatment suppressed the increased levels of inflammatory markers (COX-2, iNOS and NF-κB,) and cell proliferation markers (Cyclin-E1, Cyclin D1, VEGF, TGF-β1) exposed mice. In addition, ZnONPs-PG treatment decreased the DMBA/TPA-induced anti-apoptotic Bcl-2 protein and increasing the expression of pro-apoptotic markers (Bax and caspase 3) in skin tissues. Thus, ZnONPs-PG may prevent skin carcinogenesis through its potent antioxidant properties and inhibiting NF-κB-mediated inflammatory and proliferation pathways.

摘要

本研究调查了用灰黄青霉合成氧化锌纳米颗粒(ZnONPs-PG)及其在预防二甲基苯并蒽/十四烷酰佛波醇乙酯(DMBA/TPA)诱导的皮肤癌中的潜在作用。合成过程涉及在灰黄青霉中使用1毫摩尔二水合醋酸锌作为前体。利用包括傅里叶变换红外光谱(FTIR)、紫外可见光谱(UV-Vis)、透射电子显微镜(TEM)、X射线衍射(XRD)和动态光散射(DLS)在内的各种分析技术对ZnONPs进行表征。然后在DMBA/TPA诱导的皮肤癌模型中评估ZnONPs-PG的功效。小鼠在2周内用丙酮(200微升)中的DMBA/TPA局部处理,处理持续20周。结果显示,在DMBA/TPA处理的小鼠中肿瘤发生率为100%,有组织学变化、脂质过氧化(LPO)水平升高和抗氧化剂水平降低。然而,局部应用ZnONPs显著逆转了DMBA/TPA处理小鼠的肿瘤发生率、组织学变化、丙二醛和过氧化氢水平升高;抗氧化剂水平降低。ZnONPs-PG处理抑制了炎症标志物(COX-2、诱导型一氧化氮合酶(iNOS)和核因子κB(NF-κB))和细胞增殖标志物(细胞周期蛋白E1、细胞周期蛋白D1、血管内皮生长因子(VEGF)、转化生长因子-β1)水平升高的情况。此外,ZnONPs-PG处理降低了DMBA/TPA诱导的抗凋亡Bcl-2蛋白,并增加了皮肤组织中促凋亡标志物(Bax和半胱天冬酶3)的表达。因此,ZnONPs-PG可能通过其强大的抗氧化特性以及抑制NF-κB介导的炎症和增殖途径来预防皮肤癌发生。

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