PMID- 37493814
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230729
IS  - 2730-6011 (Electronic)
IS  - 2730-6011 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Jul 26
TI  - Antitumor activity of 5-fluorouracil polymeric nanogel synthesized by gamma 
      radiation on a rat model of colon carcinoma: a proposed mechanism.
PG  - 138
LID - 10.1007/s12672-023-00733-z [doi]
LID - 138
AB  - 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 gamma-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-kappabeta 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.
CI  - (c) 2023. The Author(s).
FAU - Abo-Zaid, Omayma A R
AU  - Abo-Zaid OAR
AUID- ORCID: 0000-0002-1752-6709
AD  - Biochemistry and Molecular Biology Department, Faculty of Vet. Med, Benha 
      University, Benha, Egypt.
FAU - Moawed, Fatma S M
AU  - Moawed FSM
AUID- ORCID: 0000-0002-5792-0815
AD  - Health Radiation Research, National Center for Radiation Research and Technology, 
      Egyptian Atomic Energy Authority, Nasr City, Cairo, 11787, Egypt. 
      fatmasearch5@yahoo.com.
FAU - Barakat, Wael E M
AU  - Barakat WEM
AD  - Biochemistry and Molecular Biology Department, Faculty of Vet. Med, Benha 
      University, Benha, Egypt.
FAU - Ghobashy, Mohamed Mohamady
AU  - Ghobashy MM
AUID- ORCID: 0000-0003-0968-1423
AD  - Radiation Research of Polymer Chemistry Department, National Center for Radiation 
      Research and Technology, Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.
FAU - Ahmed, Esraa S A
AU  - Ahmed ESA
AUID- ORCID: 0000-0001-5358-4394
AD  - Radiation Biology Research, National Center for Radiation Research and 
      Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20230726
PL  - United States
TA  - Discov Oncol
JT  - Discover oncology
JID - 101775142
PMC - PMC10371941
OTO - NOTNLM
OT  - 5-fluorouracil nanogel
OT  - AKT
OT  - Autophagy
OT  - Colon cancer
OT  - NF-kappabeta
OT  - PI3K
OT  - TLR2
OT  - mTOR
COIS- The authors declare no competing interests.
EDAT- 2023/07/26 13:07
MHDA- 2023/07/26 13:08
PMCR- 2023/07/26
CRDT- 2023/07/26 11:13
PHST- 2023/03/06 00:00 [received]
PHST- 2023/06/21 00:00 [accepted]
PHST- 2023/07/26 13:08 [medline]
PHST- 2023/07/26 13:07 [pubmed]
PHST- 2023/07/26 11:13 [entrez]
PHST- 2023/07/26 00:00 [pmc-release]
AID - 10.1007/s12672-023-00733-z [pii]
AID - 733 [pii]
AID - 10.1007/s12672-023-00733-z [doi]
PST - epublish
SO  - Discov Oncol. 2023 Jul 26;14(1):138. doi: 10.1007/s12672-023-00733-z.