The Effect of Liraglutide on Lung Cancer and Its Potential Protective Effect on High Glucose-Induced Lung Senescence and Oxidative Damage

Background: Lung cancer is a malignant disease with high morbidity and mortality. Lung cancer and diabetes are closely related, and diabetic patients with lung tumors are common in clinical practice. Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is commonly used in the treatment of type 2 diabetes. In this study, we examined the effect of liraglutide on lung cancer and its potential protective effect on high glucose-induced lung aging. Methods: Indirect mmunofluorescence was done to assess the expression levels of p-AKT, ki67, Caspase3, Bax and PI3K. Western blotting was conducted to determine the expression levels of BAX, BCL2, Caspase9, E-cadherin, N-cadherin, PI3K, AKT and vimentin. Cell viability, cell cycle and cell apoptosis were evaluated by colony formation, CCK-8 assay and flow cytometry. Immunohistochemistry was performed to evaluate the expression of Nf- $\kappa{}$ b, p15, p16, p21 and SMA in vivo. Besides, a high glucose-induced lung cell injury model was established to evaluate the effect of liraglutide on lung aging and oxidative damage. Sa- $\beta{}$ -gal staining was used to assess cellular/ tissue senescence. Cell senescence-related markers (p16, p21 and p53 ) were determined by Western-blot analysis. Results: The proliferation, cell cycle, migration of lung cancer cells were significantly inhibited after treatment with liraglutide compared to control group (p $<$ 0.05). Furthermore, Liraglutide inhibited the epithelial–mesenchymal transition process of lung cancer cell compared to control group (p $<$ 0.05). Liraglutide also suppressed the proliferation of lung cancer in vivo. Besides, the BEAS-2B cell senescence induced by high glucose was significantly alleviated after treatment with liraglutide compared with control group (p $<$ 0.05). The lung aging and endoplasmic reticulum stress was significantly suppressed after liraglutide treatment. Conclusions: This work indicates that liraglutide could inhibit lung cancer cell proliferation in vitro and in vivo. In addition, liraglutide exhibited anti-aging effects in vivo and in vivo. The current work has important implications for the treatment of patients with diabetes and lung cancer.

Keywords

liraglutide

lung cancer

proliferation

aging

lung cells

Funding

22JR5RA738/Gansu Province Science and Technology Program Project (2022) - Natural Science Foundation

31920210047/Central Universities Basic Research Business Fund (2021) - Young Teachers Innovation Project

Figures

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Fig. 1.

Liraglutide inhibited the proliferation of lung cancer cells in A549 and H1299 cell. (A) Effect of different concentrations of liraglutide (10 nmol/L–1000 nmol/L) on the proliferation of lung cancer cells (A549 and H1299). Lung cancer cells were treated with liraglutide for 48 h. (B) Effect of Liraglutide (150 nmol/L of liraglutide) on the proliferation of lung cancer cells. The cells were treated with Liraglutide (150 nmol/L) at 24–96 h. The proliferation of lung cancer cells was detected by CCK8 Kit according to the manufacturer’s instructions. The absorbance value (OD value) was measured and recorded using a microplate reader at a wavelength of 450 nm. Data were presented as mean $\pm{}$ SD. n = 3, *p $<$ 0.05, **p $<$ 0.01, ***p $<$ 0.001.

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Front. Biosci. (Landmark Ed) Print ISSN 2768-6701 Electronic ISSN 2768-6698