Angiotensin receptor blockers use and the risk of lung cancer: A meta-analysis

Zhang, Weizhen; Liang, Zhenyu; Li, Jing; Cai, Shaoxi

doi:10.1177/1470320315607391

Cited by 23 publications

(31 citation statements)

References 15 publications

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“…Studies have demonstrated that the main functions of Ang II in tumor growth are mediated by the AT1R (31). ARBs block the activation of AT1R, thus inhibiting the renin-angiotensin system (32).…”

Section: Discussionmentioning

confidence: 99%

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Zhang

Wang

2018

Oncol Lett

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Abstract. Expression of angiotensin II (Ang II), a key biological peptide in the renin-angiotensin system, is closely associated with the occurrence and development of cancer. Ang II binds two receptor subtypes, the Ang II type 1 receptor (AT1R) and the AT2R, to mediate a series of biological effects. Telmisartan, a specific AT1R blocker, has been reported to have potential as an anticancer drug for treating renal cancer. In the present study, whether telmisartan had an effect on non-small cell lung cancer (NSCLC) cell proliferation and migration was investigated. The Cell Counting kit-8 assay revealed that telmisartan significantly inhibited the growth of the NSCLC A549 cell line in a time-and dose-dependent manner. In a transwell assay, telmisartan significantly inhibited cellular invasion and migration. Furthermore, it was determined that the expression of the anti-apoptotic protein B-cell lymphoma was decreased, and that of the pro-apoptotic proteins caspase-3 and Bcl-associated X increased in the A549 cells treated with telmisartan. Additionally, levels of phosphorylated RAC serine/threonine-protein kinase (p-AKT), p-mechanistic target of rapamycin, p70-S6 kinase and cyclin D1 was decreased in the telmisartan-treated group. Therefore, the current study reveals that telmisartan-induced NSCLC apoptosis may be regulated via the phosphoinositide 3-kinase/AKT signaling pathway, which indicates that it may be a potential novel drug for clinical NSCLC treatment. IntroductionLung cancer, the most common type of cancer, has the highest morbidity rate among all types of malignancies worldwide (1,2), accounting for 30% of all incidences of cancer-associated mortality (3). In clinical practice, the two major types of lung cancer are small cell lung cancer (SCLC) and non-SCLC (NSCLC) (4), of which NSCLC accounts for ~80% of all lung cancer cases (5). Current therapies for NSCLC include chemotherapy, radiotherapy, targeted therapy and surgery, which are used alone or in combination (6). Despite the use of these therapies, the overall 5-year survival rate of NSCLC remains low, at 15% (7). Owing to the development of drug resistance and the severe side effects experienced by patients, effective and safe novel agents are required for the treatment of NSCLC (1).Angiotensin II (Ang II), a key biological peptide in the renin-angiotensin system, is a vasoconstrictor that controls cardiovascular function and renal homeostasis (8). Ang II receptor blockers (ARBs) are extensively used as anti-hypertensive drugs (9). Studies have reported that angiogenesis is essential for tumor progression and metastasis (10,11). Furthermore, studies have demonstrated that ARBs have the potential possibility to restrain the growth of several types of cancer cells (12,13). Ang II binds two receptor subtypes, the Ang II type 1 receptor (AT1R) and the Ang II type 2 receptor (AT2R), to mediate a series of biological effects (14). AT1R mediates the main functions of Ang II, including tumor growth and angiogenesis (15). Treatment with telmisartan, a spe...

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Section: Discussionmentioning

confidence: 99%

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Zhang

Wang

2018

Oncol Lett

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“…In the present study, we observed that ARB users had a significantly lower risk of lung cancer than non-ARB users. The meta-analysis of Zhang et al also demonstrated that ARBs are associated with significantly lower lung cancer risk [26]. Cohort studies conducted by Chang et al and Huang et al have also revealed that ARB use is associated with a decreased risk of lung cancer [11,27].…”

Section: Discussionmentioning

confidence: 95%

Association between Angiotensin-Converting Enzyme Inhibitors and Lung Cancer—A Nationwide, Population-Based, Propensity Score-Matched Cohort Study

Lin

et al. 2020

Cancers

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Background: Direct evidence of lung cancer risk in Asian users of angiotensin-converting enzyme inhibitors (ACEIs) is lacking. Methods: The ACEI cohort comprised 22,384 patients aged ≥ 18 years with a first prescription of ACEI. The comparison angiotensin receptor blocker (ARB) cohort consisted of age-, sex-and comorbidity-matched patients at a ratio of 1:1. The primary outcome was the incidence of lung cancer, which was evaluated using a proportional hazard model. Results: The overall incidence rates of lung cancer in the ACEI and ARB cohorts were 16.6 and 12.2 per 10,000 person-years, respectively. The ACEI cohort had a significantly higher risk of lung cancer than the ARB cohort (adjusted hazard ratio [aHR]. = 1.36; 95% confidence interval [CI]. = 1.11-1.67). Duration-response and dose-response analyses revealed that compared with patients who did not receive ACEIs, patients who received ACEIs for more than 45 days per year (aHR = 1.87; 95% CI = 1.48-2.36) and patients who received more than 540 defined daily doses of ACEIs per year (aHR =1.80; 95% CI = 1.43-2.27) had a significantly higher risk of lung cancer. The cumulative incidence of lung cancer was also significantly higher in the ACEI cohort than in the ARB cohort (log-rank test, p = 0.002). Conclusions: ACEI use is associated with an increased risk of lung cancer compared with ARB use. Patients using ARBs have a significantly lower risk of lung cancer than non-ARB users.

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“…This is supported by Yang et al, which analyzed data from almost 4 million of patients involved in six cohort studies and four case–control studies and found that ARB‐based therapy was not significantly associated with an increased risk of cancer (RR = 0.87, 95% CI: 0.75, 1.01). Some data evidence that ARBs could decrease the lung cancer risk (OR = 0.81, 95% CI: 0.69‐0.54), but subgroup analysis by race indicated that Asians treated with ARBs showed a decreased risk of lung cancer (OR = 0.60; 95% CI: 0.54‐0.67; P < 0.00001), while Caucasians did not show any significant reduction (OR = 0.90; 95% CI: 0.79‐1.02; P = 0.11) . Therefore, since the preventive role of ARBs in lung cancer is still controversial, it is possible to exclude that ARBs increase the overall risk of cancer occurrence.…”

Section: Safety Of Angiotensin Receptor Blockersmentioning

confidence: 99%

“…95% CI: 0.79-1.02; P = 0.11). 60,61 Therefore, since the preventive role of ARBs in lung cancer is still controversial, it is possible to exclude that ARBs increase the overall risk of cancer occurrence.…”

Section: Safe T Y Of Ang I Oten S In Recep Tor Blocker Smentioning

confidence: 99%

Management of arterial hypertension with angiotensin receptor blockers: Current evidence and the role of olmesartan

Omboni

Volpe

2018

Cardiovascular Therapeutics

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Summary Elevated blood pressure (BP) is a major determinant of morbidity and mortality burden related to cardio‐metabolic risk. Current guidelines indicate that controlling and lowering BP promotes cardiovascular (CV) risk reduction. Among antihypertensive agents, angiotensin receptor blockers (ARBs) are characterized by an efficacy profile equivalent to other antihypertensive agents and are provided with excellent tolerability and low discontinuation rates during chronic treatments. Moreover, CV outcomes are reduced by ARBs. Olmesartan is a long‐lasting ARB which proved to achieve a comparable or more effective action in lowering BP when compared to other ARBs. Olmesartan, in fact, displayed a larger and more sustained antihypertensive effect over the 24 hours, with a buffering effect on short‐term BP variability. These are important features which differentiate olmesartan from the other principles of the same class and that may help to control the increased CV risk in the presence of high BP variability. Olmesartan shows similar benefits as other ARBs in terms of all‐cause and CV mortality, and a favorable tolerability profile. Combination of olmesartan with long‐lasting calcium‐channel blockers and thiazide diuretics represents a rational and effective therapy. Thus, ARBs, including olmesartan, represent one of the most effective and safe treatments for patients with arterial hypertension.

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Angiotensin receptor blockers use and the risk of lung cancer: A meta-analysis

Cited by 23 publications

References 15 publications

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Association between Angiotensin-Converting Enzyme Inhibitors and Lung Cancer—A Nationwide, Population-Based, Propensity Score-Matched Cohort Study

Management of arterial hypertension with angiotensin receptor blockers: Current evidence and the role of olmesartan

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