Relationship between drugs affecting the renin-angiotensin system and colorectal cancer: The MCC-Spain study

2019 ◽

Vol 20 (4) ◽

pp. 147032031988193

Author(s):

Zhen Cheng ◽

Zhiwei Liu

Keyword(s):

Colorectal Cancer ◽

Cancer Risk ◽

Angiotensin Converting Enzyme ◽

Meta Analysis ◽

Renin Angiotensin System ◽

Recessive Model ◽

Colorectal Cancer Risk ◽

Converting Enzyme ◽

Angiotensin System ◽

Renin Angiotensin

Objective: The renin–angiotensin system gene has been implicated in the progression of colorectal cancer. Nevertheless, the details of that role remain controversial. We performed a meta-analysis to investigate the correlation between renin–angiotensin system gene polymorphisms and colorectal cancer. Methods: We retrieved relevant studies from PubMed and Embase. Subsequently, fixed or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: We identified six studies of the angiotensin-converting enzyme insertion/deletion (I/D) polymorphism, and two studies of the angiotensinogen M235T polymorphism. The angiotensin-converting enzyme I/D polymorphism did not significantly correlate with colorectal cancer risk in the total population (DD vs. II: OR 0.77, 95% CI 0.39–1.50; DI vs. II: OR 1.05, 95% CI 0.85–1.30; dominant model: OR 0.94, 95% CI 0.68–1.31; recessive model: OR 1.01, 95% CI 0.80–1.27). Similarly, the angiotensinogen M235T polymorphism was not associated with colorectal cancer risk (TT vs. MM: OR 1.38, 95% CI 0.52–3.67; TM vs. MM: OR 1.19, 95% CI 0.96–1.47; dominant model: OR 1.28, 95% CI 0.77–2.14; recessive model: OR 1.17, 95% CI 0.53–2.59). Conclusion: Our findings suggest that the angiotensin-converting enzyme I/D and angiotensinogen M235T polymorphisms are unlikely to correlate with colorectal cancer.

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Regulation of colorectal cancer cell epithelial to mesenchymal transition by the renin angiotensin system

Journal of Gastroenterology and Hepatology ◽

10.1111/jgh.13307 ◽

2016 ◽

Vol 31 (10) ◽

pp. 1773-1782 ◽

Cited By ~ 17

Author(s):

Linh Nguyen ◽

Eleanor I Ager ◽

Jaclyn Neo ◽

Christopher Christophi

Keyword(s):

Colorectal Cancer ◽

Cancer Cell ◽

Epithelial To Mesenchymal Transition ◽

Renin Angiotensin System ◽

Colorectal Cancer Cell ◽

Angiotensin System ◽

Mesenchymal Transition ◽

Renin Angiotensin

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The Potential Therapeutic Value of Renin-Angiotensin System Inhibitors in the Treatment of Colorectal Cancer

Current Pharmaceutical Design ◽

10.2174/1381612827666211011113308 ◽

2021 ◽

Vol 27 ◽

Author(s):

Ehsan Tabatabai ◽

Majid Khazaei ◽

Mohammad Reza Parizadeh ◽

Mohammad Nouri ◽

Seyed Mahdi Hassanian ◽

...

Keyword(s):

Colorectal Cancer ◽

Therapeutic Potential ◽

Critical Role ◽

Renin Angiotensin System ◽

Angiotensin Converting Enzyme Inhibitors ◽

Angiotensin Ii Receptor ◽

Converting Enzyme Inhibitors ◽

Angiotensin System ◽

Renin Angiotensin ◽

Promote Cell Proliferation

: Colorectal cancer is the third most common cancer globally. Despite extensive preclinical and clinical studies, it is still among the leading causes of cancer-related death, and a need for new therapeutic options is required. The renin-angiotensin system plays an important role in regulating blood pressure and cell growth. In addition to their hemodynamic effects, some of the renin-angiotensin system components, such as angiotensin, are also growth factors that promote cell proliferation and angiogenesis, and its dysregulation is reported to be associated with poor prognosis in colorectal cancer. Here we describe the critical role of the renin-angiotensin system pathway in colorectal cancer as well as the preclinical and clinical investigations renin-angiotensin system inhibitors: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers as a potential therapeutic target in the treatment of colorectal cancer. Several studies have been shown that the inhibition of these pathways can reduce tumor growth and metastasis; however, some of the data remain inconsistent. There is accumulating evidence of the therapeutic potential of some inhibitors, such as Losartan which are now in clinical phases in the treatment of several malignancies using Nivolumab in combination with FOLFIRINOX in pancreatic cancer. Further investigations are warranted to improve the efficacy and selectivity of current and future anticancer strategies targeting renin-angiotensin systems.

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Captopril, a Renin-Angiotensin System Inhibitor, Attenuates Features of Tumor Invasion and Down-Regulates C-Myc Expression in a Mouse Model of Colorectal Cancer Liver Metastasis

Cancers ◽

10.3390/cancers13112734 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2734

Author(s):

Georgina E. Riddiough ◽

Theodora Fifis ◽

Katrina A. Walsh ◽

Vijayaragavan Muralidharan ◽

Christopher Christophi ◽

...

Keyword(s):

Colorectal Cancer ◽

Wnt Signaling ◽

Partial Hepatectomy ◽

Target Genes ◽

Renin Angiotensin System ◽

Specific Response ◽

Liver Remnant ◽

Angiotensin System ◽

Renin Angiotensin ◽

Ras Genes

(1) Background: Recent clinical and experimental data suggests that the liver’s regenerative response following partial hepatectomy can stimulate tumor recurrence in the liver remnant. The Wnt/b-catenin pathway plays important roles in both colorectal cancer carcinogenesis and liver regeneration. Studies have shown that the Wnt/b-catenin pathway regulates multiple renin-angiotensin system (RAS) genes, whilst RAS inhibition (RASi) reduces tumor burden and progression. This study explores whether RASi attenuates features of tumor progression in the regenerating liver post-hepatectomy by modulating Wnt/b-catenin signaling. (2) Methods: Male CBA mice underwent CRLM induction, followed one week later by 70% partial hepatectomy. Mice were treated daily with captopril, a RASi, at 250mg/kg/day or vehicle control from experimental Day 4. Tumor and liver samples were analyzed for RAS and Wnt signaling markers using qRT-PCR and immunohistochemistry. (3) Results: Treatment with captopril reduced the expression of down-stream Wnt target genes, including a significant reduction in both c-myc and cyclin-D1, despite activating Wnt signaling. This was a tumor-specific response that was not elicited in corresponding liver samples. (4) Conclusions: We report for the first time decreased c-myc expression in colorectal tumors following RASi treatment in vivo. Decreased c-myc expression was accompanied by an attenuated invasive phenotype, despite increased Wnt signaling.

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Alterations in Gene Expression of Renin-Angiotensin System Components and Related Proteins in Colorectal Cancer

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1155/2021/9987115 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Danial Mehranfard ◽

Gabriela Perez ◽

Andres Rodriguez ◽

Julia M. Ladna ◽

Christopher T. Neagra ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Renin Angiotensin System ◽

Gene Expression Omnibus ◽

Data Repository ◽

Angiotensin System ◽

Renin Angiotensin ◽

Quantitative Expression ◽

Genes Encoding ◽

Thimet Oligopeptidase

Hypothesis/Introduction. Recent studies suggest involvement of the renin-angiotensin system (RAS) in cancers, including colorectal cancer (CRC). This study focuses on the association of genes encoding 17 proteins related to the RAS within a Japanese male CRC population. Materials and Methods. Quantitative expression of the RNA of these 17 genes in normal and cancerous tissues obtained using chip arrays from the public functional genomics data repository, Gene Expression Omnibus (GEO) application, was compared statistically. Results. Expression of four genes, AGT (angiotensinogen), ENPEP (aminopeptidase A) MME (neprilysin), and PREP (prolyl endopeptidase), was significantly upregulated in CRC specimens. Expression of REN (renin), THOP (thimet oligopeptidase), NLN (neurolysin), PRCP (prolyl carboxypeptidase), ANPEP (aminopeptidase N), and MAS1 (Mas receptor) was downregulated in CRC specimens. Conclusions. Presuming gene expression parallel protein expression, these results suggest that increased production of the angiotensinogen precursor of angiotensin (ANG) peptides, with the reduction of the enzymes that metabolize it to ANG II, can lead to accumulation of angiotensinogen in CRC tissues. Downregulation of THOP, NLN, PRCP, and MAS1 gene expression, whose proteins contribute to the ACE2/ANG 1-7/Mas axis, suggests that reduced activity of this RAS branch could be permissive for oncogenicity. Components of the RAS may be potential therapeutic targets for treatment of CRC.

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Renin–angiotensin system inhibitor use and colorectal cancer risk and mortality: A dose–response meta analysis

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/1470320319895646 ◽

2020 ◽

Vol 21 (3) ◽

pp. 147032031989564 ◽

Cited By ~ 1

Author(s):

Xia Chen ◽

Chang-hong Yi ◽

Kuang-guan Ya

Keyword(s):

Colorectal Cancer ◽

Cancer Risk ◽

Dose Response ◽

Meta Analysis ◽

Renin Angiotensin System ◽

Colorectal Cancer Risk ◽

Morbidity And Mortality ◽

Angiotensin System ◽

Renin Angiotensin ◽

Cancer Morbidity

Objective: This study was undertaken to determine whether use of the renin–angiotensin system (RAS) inhibitors would increase colorectal cancer morbidity and mortality. Methods: Databases were electronically searched to collect data of RAS use and colorectal cancer morbidity and mortality from inception to October 2018. Stata 12.0 software was used to perform a meta-analysis. Results: A total of 16 publications involving 2,847,597 participants were included. RAS inhibitor use was related to colorectal cancer risk (relative risk (RR): 0.86; 95% confidence interval (CI): 0.78–0.93) and mortality (RR: 0.80; 95% CI: 0.66–0.98) decrement. Subgroup analysis showed angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) (RR: 0.82; 95% CI: 0.69-0.96) or ARB (RR: 0.86; 95% CI: 0.73–0.98) or ACEI (RR: 0.81; 95% CI: 0.70–0.92) were related to colorectal cancer risk decrement. Furthermore, RAS inhibitor use was related to colorectal cancer risk decrement in Caucasians (RR: 0.88; 95% CI: 0.80–0.96) and Asians (RR: 0.72; 95% CI: 0.61–0.85). Additionally, dose–response showed that per one year duration of RAS inhibitor use incremental increase was related to 6% colorectal cancer risk decrement (RR: 0.94; 95% CI: 0.90–0.97). Conclusion: According to the evidence, RAS inhibitor use was associated with colorectal cancer risk and mortality decrement.

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