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Thymoquinone loaded calcium alginate and polyvinyl alcohol carrier inhibits the 7,12‐dimethylbenz[a]anthracene‐induced hamster oral cancer via the down‐regulation of PI3K / AKT / mTOR signaling pathways
Environmental Toxicology ( IF 4.5 ) Pub Date : 2020-10-17 , DOI: 10.1002/tox.23040
Yumei Pu 1 , Shiqi Hu 2 , Yongfeng Chen 3 , Qian Zhang 1 , Chengwan Xia 1 , Han Deng 1 , Yuxin Wang 1 , Qingang Hu 1
Affiliation  

Oral cancer is a multifactorial cancer that affects millions of peoples worldwide. The current exploration aimed to evaluate the mechanisms that thymoquinone nanoencapsulated carrier and its effects on 7,12-Dimethylbenz[a]anthracene (DMBA) stimulated hamster buccal pouch cancer in Syrian hamster model. Nanocarrier was characterized by SEM, TEM, FTIR analysis. The incidence of tumor, and biochemicals makers was studied through standard methods. The mRNA expression level of inflammatory markers NF-κBp50, NF-κBp65, and PI3K/AKT/mTOR markers in the buccal tissues of control and experimental animals were investigated through RT-PCR analysis. In thymoquinone (TQ) loaded calcium alginate and polyvinyl alcohol carrier (TQ/Ca-alg-PVA) no squamous cell carcinogenesis developed and others moderate dysplasia revealed differentiated form of hyperplasia and keratosis. In biochemical analyses with DMBA + TQ/Ca-alg-PVA (20 mg/kg bw) orally administered hamsters showed restored the antioxidants, detoxification, xenobiotic metabolising enzymes in DMBA induced plasma and oral tissues of hamsters. Further, mRNA expression level of NF-κBp50/p65 and PI3K/AKT/mTOR were upregulated in the DMBA alone painted hamster. In contrast, these expressions were down regulated in orally TQ/Ca-alg-PVA treated experimental animals. This ability more eligible to deregulate the inflammatory and PI3K/AKT/mTOR signaling pathway that proved it suppresses anti-invasion/metastasis activity during hamster buccal pouch carcinogenesis. From this study, we recommended that TQ/Ca-alg-PVA has documented as effective chemopreventive agents, in further many molecular machineries need to study.

中文翻译:

载有百里醌的海藻酸钙和聚乙烯醇载体通过下调 PI3K/AKT/mTOR 信号通路抑制 7,12-二甲基苯并[a]蒽诱导的仓鼠口腔癌

口腔癌是一种多因素癌症,影响着全世界数百万人。目前的探索旨在评估百里醌纳米胶囊载体及其对7,12-二甲基苯并[a]蒽(DMBA)的影响在叙利亚仓鼠模型中刺激仓鼠颊囊癌的机制。通过SEM、TEM、FTIR分析表征纳米载体。通过标准方法研究肿瘤和生化剂的发生率。通过RT-PCR分析研究了对照和实验动物颊组织中炎症标志物NF-κBp50、NF-κBp65和PI3K/AKT/mTOR标志物的mRNA表达水平。在含有百里醌 (TQ) 的海藻酸钙和聚乙烯醇载体 (TQ/Ca-alg-PVA) 中,未发生鳞状细胞癌变,其他中度发育不良显示分化形式的增生和角化病。在使用 DMBA + TQ/Ca-alg-PVA (20 mg/kg bw) 口服给药的仓鼠的生化分析中,DMBA 诱导的仓鼠血浆和口腔组织中的抗氧化剂、解毒、异生物质代谢酶得到恢复。此外,NF-κBp50/p65 和 PI3K/AKT/mTOR 的 mRNA 表达水平在单独涂漆仓鼠的 DMBA 中上调。相比之下,这些表达在口服 TQ/Ca-alg-PVA 治疗的实验动物中下调。这种能力更适合解除炎症和 PI3K/AKT/mTOR 信号通路的调节,证明它在仓鼠颊囊癌发生过程中抑制了抗侵袭/转移活性。从这项研究中,我们建议 TQ/Ca-alg-PVA 已被证明是有效的化学预防剂,需要进一步研究许多分子机制。
更新日期:2020-10-17
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