miR‑126/VCAM‑1 regulation by naringin suppresses cell growth of human non‑small cell lung cancer

Chen,Mingjiu; Peng,Weilin; Hu,Shifeng; Deng,Jie

doi:10.3892/ol.2018.9204

miR‑126/VCAM‑1 regulation by naringin suppresses cell growth of human non‑small cell lung cancer

Authors:
- Mingjiu Chen
- Weilin Peng
- Shifeng Hu
- Jie Deng
View Affiliations

Affiliations: Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Respiratory Medicine, The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China
Published online on: July 24, 2018 https://doi.org/10.3892/ol.2018.9204
Pages: 4754-4760

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Certain studies have indicated that naringin possesses various pharmacological activities including anti‑aging, anti‑oxidation, anticancer, cardiovascular and cerebrovascular disease prevention, in addition to anti‑hepatic effects. The present study explores the anticancer effect of naringin on human small cell lung cancer H69AR cells. Cell growth and apoptosis rates of H69AR cells were measured by MTT or flow cytometry, which demonstrated naringin suppressed cell growth and induced apoptosis of H69AR cells. MicroRNA (miR)‑126 expression and levels of phosphorylated protein kinase B (AKT), mechanistic target of rapamycin (mTOR), nuclear factor (NF)‑κB and vascular cell adhesion molecule 1 (VCAM‑1) proteins were detected by quantitative polymerase chain reaction and western blotting. It was identified that naringin increased miR‑126 expression and suppressed the phosphorylation of AKT, mTOR, NF‑κB and VCAM‑1 proteins in H69AR cells. Suppression of miR‑126 expression reduced the anticancer effects of naringin on H69AR cells, reversed the naringin‑induced reduction of phosphoinositide 3‑kinase/AKT/mTOR, and suppressed VCAM‑1 protein levels. However, close of miR‑126 expression did not affect the levels of NF‑κB protein in H69AR cells. In summary, naringin exhibits its anti‑cancer effect by suppressing cell growth of small cell lung cancer cells through miR‑126/VCAM‑1 signaling pathway.

View Figures

View References

1	Xue H, Wang H, Liu J, Liu H, Li C, Han L, Lin C, Zhan Q, Zhao Z and Qian H: MTA1 downregulation inhibits malignant potential in a small cell lung cancer cell line. Oncol Rep. 33:885–892. 2015. View Article : Google Scholar : PubMed/NCBI
2	Bremnes RM, Sundstrom S, Aasebø U, Kaasa S, Hatlevoll R and Aamdal S: Norweigian Lung Cancer Study Group: The value of prognostic factors in small cell lung cancer: Results from a randomised multicenter study with minimum 5 year follow-up. Lung Cancer. 39:303–313. 2003. View Article : Google Scholar : PubMed/NCBI
3	Wood L, Palmer M, Hewitt J, Urtasun R, Bruera E, Rapp E and Thaell JF: Results of a phase III, double-blind, placebo-controlled trial of megestrol acetate modulation of P-glycoprotein-mediated drug resistance in the first-line management of small-cell lung carcinoma. Br J Cancer. 77:627–631. 1998. View Article : Google Scholar : PubMed/NCBI
4	Barger JF and Nana-Sinkam SP: MicroRNA as tools and therapeutics in lung cancer. Respir Med. 109:803–812. 2015. View Article : Google Scholar : PubMed/NCBI
5	Che C, Zhang L, Huo J and Zhang Y: RNA interference targeting enhancer of polycomb1 exerts anti-tumor effects in lung cancer. Int J Clin Exp Pathol. 8:361–367. 2015.PubMed/NCBI
6	Joshi P, Middleton J, Jeon YJ and Garofalo M: MicroRNAs in lung cancer. World J Methodol. 4:59–72. 2014. View Article : Google Scholar : PubMed/NCBI
7	Huang Y, Hu Q, Deng Z, Hang Y, Wang J and Wang K: MicroRNAs in body fluids as biomarkers for non-small cell lung cancer: A systematic review. Technol Cancer Res Treat. 13:277–287. 2014. View Article : Google Scholar : PubMed/NCBI
8	Ferjančič Š, Gil-Bernabé AM, Hill SA, Allen PD, Richardson P, Sparey T, Savory E, McGuffog J and Muschel RJ: VCAM-1 and VAP-1 recruit myeloid cells that promote pulmonary metastasis in mice. Blood. 121:3289–3297. 2013. View Article : Google Scholar : PubMed/NCBI
9	Huang X, He D, Ming J, He Y, Zhou C, Ren H, He X, Wang C, Jin J, Ji L, et al: High-density lipoprotein of patients with breast cancer complicated with type 2 diabetes mellitus promotes cancer cells adhesion to vascular endothelium via ICAM-1 and VCAM-1 upregulation. Breast Cancer Res Treat. 155:441–455. 2016. View Article : Google Scholar : PubMed/NCBI
10	Tas F, Karabulut S, Bilgin E and Duranyildiz D: Serum levels of vascular cell adhesion molecule-1 (VCAM-1) may have diagnostic, predictive, and prognostic roles in patients with lung cancer treated with platinum-based chemotherapy. Tumour Biol. 35:7871–7875. 2014. View Article : Google Scholar : PubMed/NCBI
11	Bharti S, Rani N, Krishnamurthy B and Arya DS: Preclinical evidence for the pharmacological actions of naringin: A review. Planta Med. 80:437–451. 2014. View Article : Google Scholar : PubMed/NCBI
12	Kanno S, Shouji A, Asou K and Ishikawa M: Effects of naringin on hydrogen peroxide-induced cytotoxicity and apoptosis in P388 cells. J Pharmacol Sci. 92:166–170. 2003. View Article : Google Scholar : PubMed/NCBI
13	Camargo CA, Gomes-Marcondes MC, Wutzki NC and Aoyama H: Naringin inhibits tumor growth and reduces interleukin-6 and tumor necrosis factor α levels in rats with Walker 256 carcinosarcoma. Anticancer Res. 32:129–133. 2012.PubMed/NCBI
14	Yang J, Chen L, Ding J, Zhang J, Fan Z, Yang C, Yu Q and Yang J: Cardioprotective effect of miRNA-22 on hypoxia/reoxygenation induced cardiomyocyte injury in neonatal rats. Gene. 579:17–22. 2016. View Article : Google Scholar : PubMed/NCBI
15	Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, Ibata H, Kozuki T, Endo T, Tamura A, et al: Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 32:1902–1908. 2014. View Article : Google Scholar : PubMed/NCBI
16	Gitlitz BJ, Tsao-Wei DD, Groshen S, Davies A, Koczywas M, Belani CP, Argiris A, Ramalingam S, Vokes EE, Edelman M, et al: A phase II study of halichondrin B analog eribulin mesylate (E7389) in patients with advanced non-small cell lung cancer previously treated with a taxane: A California cancer consortium trial. J Thorac Oncol. 7:574–578. 2012. View Article : Google Scholar : PubMed/NCBI
17	Gohagan J, Marcus P, Fagerstrom R, Pinsky P, Kramer B and Prorok P: Writing Committee, Lung Screening Study Research Group: Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph: The Lung Screening Study of the National Cancer Institute. Chest. 126:114–121. 2004. View Article : Google Scholar : PubMed/NCBI
18	Zeng L, Zhen Y, Chen Y, Zou L, Zhang Y, Hu F, Feng J, Shen J and Wei B: Naringin inhibits growth and induces apoptosis by a mechanism dependent on reduced activation of NF-κB/COX-2-caspase-1 pathway in HeLa cervical cancer cells. Int J Oncol. 45:1929–1936. 2014. View Article : Google Scholar : PubMed/NCBI
19	Li H, Yang B, Huang J, Xiang T, Yin X, Wan J, Luo F, Zhang L, Li H and Ren G: Naringin inhibits growth potential of human triple-negative breast cancer cells by targeting β-catenin signaling pathway. Toxicol Lett. 220:219–228. 2013. View Article : Google Scholar : PubMed/NCBI
20	Kanno S, Shouji A, Hirata R, Asou K and Ishikawa M: Effects of naringin on cytosine arabinoside (Ara-C)-induced cytotoxicity and apoptosis in P388 cells. Life Sci. 75:353–365. 2004. View Article : Google Scholar : PubMed/NCBI
21	Zhang W, Zhang Q, Zhang M, Zhang Y, Li F and Lei P: Analysis for the mechanism between the small cell lung cancer and non-small cell lung cancer combing the miRNA and mRNA expression profiles. Thorac Cancer. 6:70–79. 2015. View Article : Google Scholar : PubMed/NCBI
22	Tan TW, Chou YE, Yang WH, Hsu CJ, Fong YC and Tang CH: Naringin suppress chondrosarcoma migration through inhibition vascular adhesion molecule-1 expression by modulating miR-126. Int Immunopharmacol. 22:107–114. 2014. View Article : Google Scholar : PubMed/NCBI
23	Fumarola C, Bonelli MA, Petronini PG and Alfieri RR: Targeting PI3K/AKT/mTOR pathway in non small cell lung cancer. Biochem Pharmacol. 90:197–207. 2014. View Article : Google Scholar : PubMed/NCBI
24	Poornima P, Weng CF and Padma VV: Neferine from Nelumbo nucifera induces autophagy through the inhibition of PI3K/Akt/mTOR pathway and ROS hyper generation in A549 cells. Food Chem. 141:3598–3605. 2013. View Article : Google Scholar : PubMed/NCBI
25	Papadimitrakopoulou V: Development of PI3K/AKT/mTOR pathway inhibitors and their application in personalized therapy for non-small-cell lung cancer. J Thorac Oncol. 7:1315–1326. 2012. View Article : Google Scholar : PubMed/NCBI
26	Choi UJ, Jee BK, Lim Y and Lee KH: KAI1/CD82 decreases Rac1 expression and cell proliferation through PI3K/Akt/mTOR pathway in H1299 lung carcinoma cells. Cell Biochem Funct. 27:40–47. 2009. View Article : Google Scholar : PubMed/NCBI
27	Lee EJ, Kim DI, Kim WJ and Moon SK: Naringin inhibits matrix metalloproteinase-9 expression and AKT phosphorylation in tumor necrosis factor-alpha-induced vascular smooth muscle cells. Mol Nutr Food Res. 53:1582–1591. 2009. View Article : Google Scholar : PubMed/NCBI
28	Visweswaran GR, Gholizadeh S, Ruiters MH, Molema G, Kok RJ and Kamps JA: Targeting rapamycin to podocytes using a Vascular Cell Adhesion Molecule-1 (VCAM-1)-harnessed SAINT-based lipid carrier system. PLoS One. 10:e01388702015. View Article : Google Scholar : PubMed/NCBI
29	Yurdagul A Jr, Sulzmaier FJ, Chen XL, Pattillo CB, Schlaepfer DD and Orr AW: Oxidized LDL induces FAK-dependent RSK signaling to drive NF-κB activation and VCAM-1 expression. J Cell Sci. 129:1580–1591. 2016. View Article : Google Scholar : PubMed/NCBI
30	Gong L, Mi HJ, Zhu H, Zhou X and Yang H: P-selectin-mediated platelet activation promotes adhesion of non-small cell lung carcinoma cells on vascular endothelial cells under flow. Mol Med Rep. 5:935–942. 2012. View Article : Google Scholar : PubMed/NCBI