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尼美舒利纳米颗粒能否成为抑制胰腺癌中KRAS/PTEN信号通路的治疗策略？

Can Nimesulide Nanoparticles Be a Therapeutic Strategy for the Inhibition of the KRAS/PTEN Signaling Pathway in Pancreatic Cancer?

作者信息

Ferreira Roseane Guimarães, Narvaez Luis Eduardo Mosquera, Espíndola Kaio Murilo Monteiro, Rosario Amanda Caroline R S, Lima Wenddy Graziela N, Monteiro Marta Chagas

机构信息

Neuroscience and Cell Biology Post-Graduation Program, Laboratory of In Vitro Tests, Immunology and Microbiology-LABEIM, Biological Sciences Institute, Federal University of Pará/UFPA, Belém, Brazil.

Pharmaceutical Science Post-Graduation Program, Laboratory of In Vitro Tests, Immunology and Microbiology-LABEIM, Health Science Institute, Federal University of Pará/UFPA, Belém, Brazil.

出版信息

Front Oncol. 2021 Jul 20;11:594917. doi: 10.3389/fonc.2021.594917. eCollection 2021.

DOI:10.3389/fonc.2021.594917
PMID:34354940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8329661/
Abstract

Pancreatic cancer is an aggressive, devastating disease due to its invasiveness, rapid progression, and resistance to surgical, pharmacological, chemotherapy, and radiotherapy treatments. The disease develops from PanINs lesions that progress through different stages. KRAS mutations are frequently observed in these lesions, accompanied by inactivation of PTEN, hyperactivation of the PI3K/AKT pathway, and chronic inflammation with overexpression of COX-2. Nimesulide is a selective COX-2 inhibitor that has shown anticancer effects in neoplastic pancreatic cells. This drug works by increasing the levels of PTEN expression and inhibiting proliferation and apoptosis. However, there is a need to improve nimesulide through its encapsulation by solid lipid nanoparticles to overcome problems related to the hepatotoxicity and bioavailability of the drug.

摘要

胰腺癌是一种侵袭性强、具有毁灭性的疾病，因其具有侵袭性、进展迅速，且对手术、药理学、化疗和放疗治疗具有抗性。该疾病由胰腺上皮内瘤变（PanINs）病变发展而来，这些病变会经历不同阶段。KRAS突变在这些病变中经常出现，同时伴有PTEN失活、PI3K/AKT通路过度激活以及COX - 2过表达引起的慢性炎症。尼美舒利是一种选择性COX - 2抑制剂，已在胰腺肿瘤细胞中显示出抗癌作用。这种药物通过增加PTEN表达水平以及抑制增殖和凋亡来发挥作用。然而，需要通过将尼美舒利用固体脂质纳米粒包封来改进它，以克服与该药物的肝毒性和生物利用度相关的问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d978/8329661/4c823dd359e5/fonc-11-594917-g006.jpg
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