In Vivo and In Vitro Enhanced Tumoricidal Effects of Metformin, Active Vitamin D3, and 5-Fluorouracil Triple Therapy against Colon Cancer by Modulating the PI3K/Akt/PTEN/mTOR Network
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Experimental Animal Studies and Treatment Protocols
2.2.1. Gross Examination and Tumour Counting
2.2.2. Histopathological Studies of Colon Tissues
2.2.3. Immunohistochemistry (IHC)
2.2.4. Terminal Deoxynucleotidyl Transferase-dUTP Nick End Labelling (TUNEL) Assay
2.2.5. Liver and Renal Biochemical Profiles
2.2.6. ELISA
2.3. Cell Culture and Treatment Protocols
2.3.1. Cell Cycle Analysis
2.3.2. Apoptosis Assay
2.3.3. Quantitative Reverse-Transcription Polymerase Chain Reaction
2.3.4. Western Blot
2.4. Statistical Analysis
3. Results
3.1. Effects of Treatment Regimens on CRC Progression in Mice
3.2. Effects of the Different Treatment Protocols on Cell Cycle
3.2.1. In Vivo Expression of CCND1 and p21
3.2.2. In Vitro Cell Cycle Arrest and Expression of Cell Cycle Regulatory Molecules
3.3. Effects of the Different Treatment Protocols on Cell Death and Apoptosis Markers
3.3.1. Colonic Cell Apoptosis and Apoptosis Markers In Vivo
3.3.2. In Vitro Cell Apoptosis and Expression of Apoptosis Markers
3.4. Effects of the Different Treatment Protocols on the Expression of PI3K/Akt/mTOR Oncogenic Pathway
3.4.1. Protein Expression of PI3K/Akt/mTOR in Colonic Tissues
3.4.2. In Vitro Gene and Protein Expression of the PI3K/Akt/mTOR Oncogenic Pathway
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Almaimani, R.A.; Aslam, A.; Ahmad, J.; El-Readi, M.Z.; El-Boshy, M.E.; Abdelghany, A.H.; Idris, S.; Alhadrami, M.; Althubiti, M.; Almasmoum, H.A.; et al. In Vivo and In Vitro Enhanced Tumoricidal Effects of Metformin, Active Vitamin D3, and 5-Fluorouracil Triple Therapy against Colon Cancer by Modulating the PI3K/Akt/PTEN/mTOR Network. Cancers 2022, 14, 1538. https://doi.org/10.3390/cancers14061538
Almaimani RA, Aslam A, Ahmad J, El-Readi MZ, El-Boshy ME, Abdelghany AH, Idris S, Alhadrami M, Althubiti M, Almasmoum HA, et al. In Vivo and In Vitro Enhanced Tumoricidal Effects of Metformin, Active Vitamin D3, and 5-Fluorouracil Triple Therapy against Colon Cancer by Modulating the PI3K/Akt/PTEN/mTOR Network. Cancers. 2022; 14(6):1538. https://doi.org/10.3390/cancers14061538
Chicago/Turabian StyleAlmaimani, Riyad Adnan, Akhmed Aslam, Jawwad Ahmad, Mahmoud Zaki El-Readi, Mohamed E. El-Boshy, Abdelghany H. Abdelghany, Shakir Idris, Mai Alhadrami, Mohammad Althubiti, Hussain A. Almasmoum, and et al. 2022. "In Vivo and In Vitro Enhanced Tumoricidal Effects of Metformin, Active Vitamin D3, and 5-Fluorouracil Triple Therapy against Colon Cancer by Modulating the PI3K/Akt/PTEN/mTOR Network" Cancers 14, no. 6: 1538. https://doi.org/10.3390/cancers14061538