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: Faruk M; Department of Pathology, Faculty of Basic Clinical Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria., Ibrahim S; Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria., Aminu SM; Department of Haematology and Blood Transfusion, Faculty of Basic Clinical Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria., Adamu A; Department of Surgery, Faculty of Basic Clinical Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria., Abdullahi A; Department of Radiotherapy and Oncology, College of Medical Sciences, Faculty of Basic Clinical Sciences, Ahmadu Bello University, Zaria, Nigeria., Suleiman AM; Department of Haematology and Blood Transfusion, Faculty of Basic Clinical Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria., Rafindadi AH; Department of Pathology, Faculty of Basic Clinical Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria., Mohammed A; Department of Pathology, Faculty of Basic Clinical Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria., Iliyasu Y; Department of Pathology, Faculty of Basic Clinical Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria., Idoko J; Department of Pathology, Faculty of Basic Clinical Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria., Saidu R; Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Ilorin, Ilorin, Nigeria.; Department of Obstetrics and Gynaecology, University of Cape Town, Cape Town, South Africa., Randawa AJ; Department of Obstetrics and Gynaecology, Faculty of Clinical Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria., Musa HS; Department of Veterinary Surgery and Radiology, Veterinary Teaching Hospital, Ahmadu Bello University Zaria, Zaria, Nigeria., Ntekim A; Department of Radiation Oncology, College of Medicine, University of Ibadan, Ibadan, Nigeria., Shah KZ; Nova Medical Centre, Lahore, Pakistan., Abubakar S; Department of Pathology, Aminu Kano University Teaching Hospital, Kano, Nigeria., Adoke KU; Department of Pathology, Federal Medical Centre, Birnin Kebbi, Nigeria., Manko M; Department of Medicine, Faculty of Clinical Sciences, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria., Awasum CA; Department of Veterinary Surgery and Radiology, Veterinary Teaching Hospital, Ahmadu Bello University Zaria, Zaria, Nigeria.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2021 Jan 19; Vol. 16 (1), pp. e0245581. Date of Electronic Publication: 2021 Jan 19 (Print Publication: 2021).
DOI: 10.1371/journal.pone.0245581
Abstrakt: 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 treatment in vivo in 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 treatments in vivo (p <0.05). The mechanistic rational of these effects underscores the importance of expanded concept of possible aspirin combination therapy with FOLFOX sequentially in future CRC management. Validation of our findings through randomized clinical trials of aspirin plus FOLFOX sequentially in patients with CRC is therefore warranted.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje