Inhibition of APLN suppresses cell proliferation and migration and promotes cell apoptosis in esophageal cancer cells in vitro, through activating PI3K/mTOR signaling pathway

Submitted: 1 October 2021
Accepted: 13 July 2022
Published: 3 August 2022
Abstract Views: 834
PDF: 505
HTML: 20
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Esophageal cancer is the sixth leading cause of cancer mortalities globally with a high incidence rate. Apelin (APLN) plays regulatory roles in different organs. However, its role in esophageal cancer remains unknown. Therefore, our study aims to explore the effect of APLN on esophageal cancer. One hundred and eighty-four (184) esophageal tumor tissues samples from patients with esophageal cancer, and 11 esophageal tissues samples from healthy volunteers were analyzed for the expression of APLN. APLN was highly expressed in the tumor of patients with esophageal cancer and esophageal cancer cells.  Patients with high expressions of APLN had a lower survival rate than the ones with low to medium expressions of APLN.  Human esophageal carcinoma cell lines, TE-1 and ECA-109 cells were transfected with APLN siRNA to knockdown APLN, or transfected with pcDNA-APLN to overexpress APLN. Inhibition of APLN by siRNA-APLN reduced proliferative, migrative, and invasive abilities of esophageal cancer cells and promoted cell apoptosis, which could be all restored by pcDNA-APLN. Moreover, knocking down APLN by siRNA-APLN suppressed the PI3K/mTOR signaling pathway. These findings identify that APLN inhibition might ameliorate esophageal cancer through activating the PI3K/mTOR signaling pathway, thus APLN could be a potential target for esophageal cancer.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med 2003;349:2241-52. DOI: https://doi.org/10.1056/NEJMra035010
Zhang Y. Epidemiology of esophageal cancer. World J Gastroenterol 2013;19:5598. DOI: https://doi.org/10.3748/wjg.v19.i34.5598
O'Dowd BF, Heiber M, Chan A, Heng HH, Tsui LC, Kennedy JL, et al. A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene 1993;136:355-60. DOI: https://doi.org/10.1016/0378-1119(93)90495-O
Szokodi I, Tavi P, Földes G, Voutilainen-Myllylä S, Ilves M, Tokola H, et al. Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility. Circ Res 2002;91:434-40. DOI: https://doi.org/10.1161/01.RES.0000033522.37861.69
Huang J, Koulaouzidis A, Marlicz W, Lok V, Chu C, Ngai CH, et al. Global burden, risk factors, and trends of esophageal cancer: An analysis of cancer registries from 48 countries. Cancers 2021;13:141. DOI: https://doi.org/10.3390/cancers13010141
Wong MC, Hamilton W, Whiteman DC, Jiang JY, Qiao Y, Fung FD, et al. Global Incidence and mortality of oesophageal cancer and their correlation with socioeconomic indicators temporal patterns and trends in 41 countries. Sci Rep 2018;8:1-13. DOI: https://doi.org/10.1038/s41598-018-19819-8
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2095-128. DOI: https://doi.org/10.1016/S0140-6736(12)61728-0
Lee DK, Cheng R, Nguyen T, Fan T, Kariyawasam AP, Liu Y, et al. Characterization of apelin, the ligand for the APJ receptor. J Neurochem 2000;74:34-41. DOI: https://doi.org/10.1046/j.1471-4159.2000.0740034.x
Antushevich H, Wójcik M. Review: Apelin in disease. Clin Chim Acta 2018;483:241-8. DOI: https://doi.org/10.1016/j.cca.2018.05.012
Chen H, Wong CC, Liu D, Go MYY, Wu B, Peng S, et al. APLN promotes hepatocellular carcinoma through activating PI3K/Akt pathway and is a druggable target. Theranostics 2019;9:5246-60. DOI: https://doi.org/10.7150/thno.34713
Liu Z, Iyer MR, Godlewski G, Jourdan T, Liu J, Coffey NJ, et al. Functional selectivity of a biased cannabinoid-1 receptor (CB(1)R) antagonist. ACS Pharmacol Transl Sci 2021;4:1175-87. DOI: https://doi.org/10.1021/acsptsci.1c00048
Ma Y, Yu S, Zhao W, Lu Z, Chen J. miR-27a regulates the growth, colony formation and migration of pancreatic cancer cells by targeting Sprouty2. Cancer Lett 2010;298:150-8. DOI: https://doi.org/10.1016/j.canlet.2010.06.012
Liu Z, Luo H, Zhang L, Huang Y, Liu B, Ma K, et al. Hyperhomocysteinemia exaggerates adventitial inflammation and angiotensin II-induced abdominal aortic aneurysm in mice. Circ Res 2012;111:1261-73. DOI: https://doi.org/10.1161/CIRCRESAHA.112.270520
Chen S, Cheng A-C, Wang M-S, Peng X. Detection of apoptosis induced by new type gosling viral enteritis virus in vitro through fluorescein annexin V-FITC/PI double labeling. World J Gastroenterol 2008;14:2174. DOI: https://doi.org/10.3748/wjg.14.2174
Yang Y, Lv SY, Ye W, Zhang L. Apelin/APJ system and cancer. Clin Chim Acta 2016;457:112-6. DOI: https://doi.org/10.1016/j.cca.2016.04.001
Chen Y, Lin X, Zheng J, Chen J, Xue H, Zheng X. APLN: A potential novel biomarker for cervical cancer. Sci Prog 2021;104:368504211011341. DOI: https://doi.org/10.1177/00368504211011341
Masoumi J, Jafarzadeh A, Khorramdelazad H, Abbasloui M, Abdolalizadeh J, Jamali N. Role of apelin/APJ axis in cancer development and progression. Adv Med Sci 2020;65:202-13. DOI: https://doi.org/10.1016/j.advms.2020.02.002

Ethics Approval

This study was approved by the Ethic Committee of Shanghai Chest Hospital, Shanghai Jiaotong University, China

Rights

National Natural Science Foundation of China; Three-year action plan for Shanghai to further accelerate the development of Chinese Medicine; third Round of Chinese Medicine Action Plan - Major Clinical Research Projects in Traditional Chinese Medicine; Interdisciplinary Program of Shanghai Jiao Tong University

How to Cite

Wang, Y., Wang, G., Liu, X., Yun, D., Cui, Q., Wu, X., … Zhang, M. (2022). Inhibition of APLN suppresses cell proliferation and migration and promotes cell apoptosis in esophageal cancer cells <em>in vitro</em>, through activating PI3K/mTOR signaling pathway. European Journal of Histochemistry, 66(3). https://doi.org/10.4081/ejh.2022.3336

Similar Articles

<< < 49 50 51 52 53 54 55 56 57 > >> 

You may also start an advanced similarity search for this article.