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

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.

Methoxybenzamide derivative of nimesulide from anti-fever to anti-cancer: Chemical characterization and cytotoxicity

“…In this study, agent L1 is found to be soluble in solvents such as methanol, ethanol, DMSO, CHCl 3 , acetone, and water ( Ferreira et al, 2021 ). Agent L1 purity was tested by elemental analysis, FTIR, 1H NMR, and 13C NMR.…”

Targeted Nanoparticle-Based Diagnostic and Treatment Options for Pancreatic Cancer

“…A recent study proposed a formulation encapsulating nimesulide, an NSAID and potential inhibitor of the KRAS/PTEN signaling pathway, in SLNs. This method aims to boost bioavailability, reduce hepatotoxicity, and inhibit cell growth in PanIN cells by increasing PTEN levels [177]. In order to improve the efficacy of the PDAC standard treatment drug gemcitabine, a 2019 study evaluated the impact of a gemcitabine-loaded SLN (Gem-SLN) on MiaPaCa-2 and patient-derived primary pancreatic cancer cell lines (PPCL-46).…”

Contribuição Do Diagnóstico Por Imagem Para a Ciência Forense

“…O nimesulide apresenta efeito supressor nas células cancerígenas e ação antiproliferativa, sendo capaz de estimular apoptose em câncer mamário (FERREIRA et al, 2021). Em estudos com ratas com câncer mamário induzido, Nakatsugi et al (2000) demonstraram que o nimesulide foi capaz de suprimir a evolução da doença, provocando redução no tamanho e na proliferação dos carcinomas.…”