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
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
|---|---|
| Enthalten in: |
PloS one - 16(2021), 1 vom: 19., Seite e0245581 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Faruk, Mohammed [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 10.06.2021 Date Revised 10.06.2021 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.1371/journal.pone.0245581 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM320275531 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM320275531 | ||
| 003 | DE-627 | ||
| 005 | 20231225173229.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1371/journal.pone.0245581 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1067.xml |
| 035 | |a (DE-627)NLM320275531 | ||
| 035 | |a (NLM)33465114 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Faruk, Mohammed |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 10.06.2021 | ||
| 500 | |a Date Revised 10.06.2021 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a ACKR1 protein, human |2 NLM | |
| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 650 | 7 | |a Annexin A5 |2 NLM | |
| 650 | 7 | |a B7-H1 Antigen |2 NLM | |
| 650 | 7 | |a BIRC7 protein, human |2 NLM | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a Duffy Blood-Group System |2 NLM | |
| 650 | 7 | |a Inhibitor of Apoptosis Proteins |2 NLM | |
| 650 | 7 | |a Neoplasm Proteins |2 NLM | |
| 650 | 7 | |a Organoplatinum Compounds |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-bcl-2 |2 NLM | |
| 650 | 7 | |a Receptors, Cell Surface |2 NLM | |
| 650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
| 650 | 7 | |a MSH2 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.6.1.3 |2 NLM | |
| 650 | 7 | |a Mismatch Repair Endonuclease PMS2 |2 NLM | |
| 650 | 7 | |a EC 3.6.1.3 |2 NLM | |
| 650 | 7 | |a MutS Homolog 2 Protein |2 NLM | |
| 650 | 7 | |a EC 3.6.1.3 |2 NLM | |
| 650 | 7 | |a Leucovorin |2 NLM | |
| 650 | 7 | |a Q573I9DVLP |2 NLM | |
| 650 | 7 | |a Aspirin |2 NLM | |
| 650 | 7 | |a R16CO5Y76E |2 NLM | |
| 650 | 7 | |a Fluorouracil |2 NLM | |
| 650 | 7 | |a U3P01618RT |2 NLM | |
| 700 | 1 | |a Ibrahim, Sani |e verfasserin |4 aut | |
| 700 | 1 | |a Aminu, Surajo Mohammed |e verfasserin |4 aut | |
| 700 | 1 | |a Adamu, Ahmed |e verfasserin |4 aut | |
| 700 | 1 | |a Abdullahi, Adamu |e verfasserin |4 aut | |
| 700 | 1 | |a Suleiman, Aishatu Maude |e verfasserin |4 aut | |
| 700 | 1 | |a Rafindadi, Abdulmumini Hassan |e verfasserin |4 aut | |
| 700 | 1 | |a Mohammed, Abdullahi |e verfasserin |4 aut | |
| 700 | 1 | |a Iliyasu, Yawale |e verfasserin |4 aut | |
| 700 | 1 | |a Idoko, John |e verfasserin |4 aut | |
| 700 | 1 | |a Saidu, Rakiya |e verfasserin |4 aut | |
| 700 | 1 | |a Randawa, Abdullahi Jibril |e verfasserin |4 aut | |
| 700 | 1 | |a Musa, Halimatu Sadiya |e verfasserin |4 aut | |
| 700 | 1 | |a Ntekim, Atara |e verfasserin |4 aut | |
| 700 | 1 | |a Shah, Khalid Zahir |e verfasserin |4 aut | |
| 700 | 1 | |a Abubakar, Sani |e verfasserin |4 aut | |
| 700 | 1 | |a Adoke, Kasimu Umar |e verfasserin |4 aut | |
| 700 | 1 | |a Manko, Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Awasum, Cheh Agustin |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t PloS one |d 2006 |g 16(2021), 1 vom: 19., Seite e0245581 |w (DE-627)NLM167327399 |x 1932-6203 |7 nnns |
| 773 | 1 | 8 | |g volume:16 |g year:2021 |g number:1 |g day:19 |g pages:e0245581 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1371/journal.pone.0245581 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 16 |j 2021 |e 1 |b 19 |h e0245581 | ||