Prognostic significance of BIRC7/Livin, Bcl-2, p53, Annexin V, PD-L1, DARC, MSH2 and PMS2 in colorectal cancer treated with FOLFOX chemotherapy with or without aspirin

Autor: Muhammad Manko, John Idoko, Kasimu Umar Adoke, Adamu Abdullahi, Abdullahi Mohammed, Surajo Mohammed Aminu, Sani Abubakar, Sani Ibrahim, Yawale Iliyasu, Halimatu Sadiya Musa, Khalid Zahir Shah, Ahmed Adamu, Aishatu Maude Suleiman, Mohammed Faruk, Abdulmumini Hassan Rafindadi, Cheh Agustin Awasum, Rakiya Saidu, Abdullahi Jibril Randawa, Atara Ntekim
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Organoplatinum Compounds
Colorectal cancer
medicine.medical_treatment
Protein Expression
Cancer Treatment
Leucovorin
Apoptosis
Aminotransferases
Biochemistry
DNA Mismatch Repair
B7-H1 Antigen
Metastasis
Inhibitor of Apoptosis Proteins
FOLFOX
Antineoplastic Combined Chemotherapy Protocols
Medicine and Health Sciences
Drug Interactions
Annexin A5
Mismatch Repair Endonuclease PMS2
Multidisciplinary
Cell Death
Prognosis
Enzymes
Neoplasm Proteins
Chemistry
MutS Homolog 2 Protein
Oncology
Proto-Oncogene Proteins c-bcl-2
Cell Processes
Barium
Physical Sciences
Medicine
Fluorouracil
Anatomy
Colorectal Neoplasms
medicine.drug
Research Article
Chemical Elements
Histology
Combination therapy
Colon
Science
Receptors
Cell Surface
Research and Analysis Methods
Folinic acid
Transferases
Cell Line
Tumor
medicine
Gene Expression and Vector Techniques
Biomarkers
Tumor
Animals
Humans
Molecular Biology Techniques
Molecular Biology
Adaptor Proteins
Signal Transducing
Colorectal Cancer
Chemotherapy
Molecular Biology Assays and Analysis Techniques
Aspirin
business.industry
Cancers and Neoplasms
Biology and Life Sciences
Proteins
Cell Biology
medicine.disease
Xenograft Model Antitumor Assays
digestive system diseases
Oxaliplatin
Rats
Gastrointestinal Tract
MSH2
Cancer research
Enzymology
Tumor Suppressor Protein p53
business
Duffy Blood-Group System
Digestive System
Zdroj: PLoS ONE, Vol 16, Iss 1, p e0245581 (2021)
PLoS ONE
BASE-Bielefeld Academic Search Engine
ISSN: 1932-6203
Popis: Evasion of apoptosis is associated with treatment resistance and metastasis in colorectal cancer (CRC). Various cellular processes are associated with evasion of apoptosis. These include overexpression of pro-apoptotic proteins (including p53 and PD-L1), anti-apoptotic proteins (BIRC7/Livin and Bcl-2), chemokine receptors (including DARC), and dysregulation of DNA mismatch repair proteins (including MSH2 and PMS2). The aim of this study was to determine the effect of folinic acid, 5-FU and oxaliplatin (FOLFOX) as a single agent and aspirin plus FOLFOX in various combinations on the aforementioned proteins in human CRC, SW480 cell line and rat models of N-Methyl-N-Nitrosourea (NMU)-induced CRC. In addition, effects of the NMU-induced CRC and chemotherapeutic regimens on haematological and biochemical parameters in the rat models were studied. Immunohistochemistry, immunofluorescence and immunoblot techniques were used to study the expression pattern of the related proteins in the human CRC cells pre- and post-treatment. Double contrast barium enema, post-mortem examination and histological analyses were used to confirm tumour growth and the effect of the treatmentin vivoin rat models. Notably, we found in human mucinous CRC, a significant increase in expression of the BIRC7/Livin post-FOLFOX treatment compared with pre-treatment (p= 0.0001). This increase provides new insights into the prognostic role of BIRC7/Livin in evasion of apoptosis and facilitation of treatment resistance, local recurrence and metastasis particularly among mucinous CRCs post-FOLFOX chemotherapy. These poor prognostic features in the CRC may be further compounded by the significant suppression of DARC, PD-L1, PMS2 and overexpression of MSH2 and anti-apoptotic Bcl-2 and p53 proteins observed in our study (p < 0.05). Importantly, we found a significant reduction in expression of BIRC7/Livin and reactivation of DARC and PD-L1 with a surge in Annexin V expression in rat models of CRC cells post-treatment with a sequential dose of aspirin plus FOLFOX compared with other treatmentsin vivo(p
Databáze: OpenAIRE
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