Antitumor activity of 5-fluorouracil polymeric nanogel synthesized by gamma radiation on a rat model of colon carcinoma: a proposed mechanism.

Autor: Abo-Zaid OAR; Biochemistry and Molecular Biology Department, Faculty of Vet. Med, Benha University, Benha, Egypt., Moawed FSM; Health Radiation Research, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Nasr City, Cairo, 11787, Egypt. fatmasearch5@yahoo.com., Barakat WEM; Biochemistry and Molecular Biology Department, Faculty of Vet. Med, Benha University, Benha, Egypt., Ghobashy MM; Radiation Research of Polymer Chemistry Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt., Ahmed ESA; Radiation Biology Research, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Discover. Oncology [Discov Oncol] 2023 Jul 26; Vol. 14 (1), pp. 138. Date of Electronic Publication: 2023 Jul 26.
DOI: 10.1007/s12672-023-00733-z
Abstrakt: The use of 5-fluorouracil (5-FU) is associated with multifaceted challenges and poor pharmacokinetics. Accordingly, our study was designed to prepare 5-FU nanogel as a new form of the colon cancer chemotherapeutic drug 5-FU using polyacrylic acid and gelatin hybrid nanogel as efficient drug carriers. Alongside the in vivo chemotherapeutic evaluation, the anti-proliferative and anti-apoptotic efficacy were carried out for 5-FU nanogel against 1,2-dimethylhydrazine (DMH, 20 mg/kg) and γ-radiation (4 Gy)-prompted colon dysplasia in rats compared to 5-FU. The morphology and size of 5-FU nanogel were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) in addition to cytotoxicity assay. The expression of phosphoinositide-3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR); Toll-like receptor2 (TLR2)/nuclear factor kappa B), adenosine monophosphate (AMP)-activated protein kinase (AMPK) and its downstream autophagy-related genes in addition to apoptotic markers were measured in colon tissues. Results: 5-FU nanogel reduced the levels of the TLR2/ NF-κβ as well as the expression of PI3K/AKT/mTOR. Moreover, it promoted autophagy through the activation of the AMPK and its downstream targets which consequently augmented the intrinsic and extrinsic apoptotic pathways. Conclusion: Collectively, these data might strengthen the therapeutic potential of 5-FU nanogel which can be used as an antitumor product for colon cancer.
(© 2023. The Author(s).)
Databáze: MEDLINE
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