Total flavonoids suppress lung cancer growth via the COX‑2‑mediated Wnt/β‑catenin signaling pathway Retraction in /10.3892/ol.2024.14212

Han,Lei; Fang,Shu; Li,Guangtao; Wang,Minghuan; Yu,Renzhi

doi:10.3892/ol.2020.11271

Total flavonoids suppress lung cancer growth via the COX‑2‑mediated Wnt/β‑catenin signaling pathway

Retraction in: /10.3892/ol.2024.14212

Authors:
- Lei Han
- Shu Fang
- Guangtao Li
- Minghuan Wang
- Renzhi Yu
View Affiliations

Affiliations: Department of Respiratory Medicine, Mudanjiang Medical University Affiliated Hongqi Hospital, Mudanjiang, Heilongjiang 157000, P.R. China, Community Health Service Center, Mudanjiang Medical University Affiliated Hongqi Hospital, Mudanjiang, Heilongjiang 157000, P.R. China, Department of Respiratory Medicine, Kangan Hospital, Mudanjiang, Heilongjiang 157000, P.R. China
Published online on: January 9, 2020 https://doi.org/10.3892/ol.2020.11271
Pages: 1824-1830
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

The aim of the present study was to explore the anti‑cancer effects of total flavonoids (TF) on lung cancer and to investigate the underlying mechanism. The inhibitory effect of TF on the proliferation of A549 cells in vitro was measured using an MTT assay. The apoptotic rate of TF‑treated A549 cells was analyzed using flow cytometry and terminal deoxynucleotidyl transferase‑mediated biotinylated UTP nick end labeling. Migration and invasion assays were performed to investigate the anti‑migration effect of TF on A549 cells. Reverse‑transcription quantitative PCR was used to analyze BCL2‑like 2, BCL2, Bax, Bad, cyclooxygenase 2 (COX‑2), Wnt and β‑catenin mRNA expression levels in A549 cells. The in vivo anti‑cancer effect of TF was investigated in a subcutaneous xenograft model of lung cancer in BALB/c nude mice. The results obtained in the present study revealed that TF exerted a significant inhibitory effect on the proliferation of A549 cells in a dose‑dependent manner (P<0.01). TF induced apoptosis of A549 cells, which exhibited increased and decreased expression of pro‑ and anti‑ apoptotic genes, respectively. Furthermore, TF had a significant inhibitory effect on the migration and invasion of A549 cells (P<0.01). The mRNA expression levels of COX‑2, Wnt and β‑catenin were significantly downregulated in TF‑treated A549 cells compared with controls. Additionally, treatment with TF inhibited tumor growth in mice, with a tumor inhibition rate of 64.07% compared with the controls. TF exhibited significant tumor inhibitory effects in vivo by promoting the apoptosis of tumor cells. In conclusion, the results suggested that TF may regulate lung cancer growth via the COX‑2‑Wnt/β‑catenin signaling pathway. TF may serve as a novel anti‑cancer agent for the treatment of lung cancer.

View Figures

View References

1	Loganadane G, Martinetti F, Mercier O, Krhili S, Riet FG, Mbagui R, To H, Le Péchoux C and Levy A: Stereotactic ablative radiotherapy for early stage non-small cell lung cancer: A critical literature review of predictive factors of relapse. Cancer Treat Rev. 50:240–246. 2016. View Article : Google Scholar : PubMed/NCBI
2	Sun G, Liu B, He J, Zhao X and Li B: Expression of EGFR is closely related to reduced 3-year survival rate in Chinese female NSCLC. Med Sci Monit. 21:2225–2231. 2015. View Article : Google Scholar : PubMed/NCBI
3	Xiao J, Hu CP, He BX, Chen X, Lu XX, Xie MX, Li W, He SY, You SJ and Chen Q: PTEN expression is a prognostic marker for patients with non-small cell lung cancer: A systematic review and meta-analysis of the literature. Oncotarget. 7:57832–57840. 2016. View Article : Google Scholar : PubMed/NCBI
4	Li SJ, Huang J, Zhou XD, Zhang WB, Lai YT and Che GW: Clinicopathological and prognostic significance of Oct-4 expression in patients with non-small cell lung cancer: A systematic review and meta-analysis. J Thorac Dis. 8:1587–1600. 2016. View Article : Google Scholar : PubMed/NCBI
5	Lim JS and Soo RA: Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: A review of the evidence. Ther Adv Respir Dis. 10:444–454. 2016. View Article : Google Scholar : PubMed/NCBI
6	Chen J, Wu X, Shi T and Kang M: Efficacy of targeted agents in the treatment of elderly patients with advanced non-small-cell lung cancer: A systematic review and meta-analysis. Onco Targets Ther. 9:4797–4803. 2016. View Article : Google Scholar : PubMed/NCBI
7	Stewart EL, Tan SZ, Liu G and Tsao MS: Known and putative mechanisms of resistance to EGFR targeted therapies in NSCLC patients with EGFR mutations-A review. Transl Lung Cancer Res. 4:67–81. 2015.PubMed/NCBI
8	Zhou JG, Tian X, Wang X, Tian JH, Wang Y, Wang F, Zhang Y and Ma H: Treatment on advanced NSCLC: Platinum-based chemotherapy plus erlotinib or platinum-based chemotherapy alone? A systematic review and meta-analysis of randomised controlled trials. Med Oncol. 32:4712015. View Article : Google Scholar : PubMed/NCBI
9	Lange A, Prenzler A, Frank M, Golpon H, Welte T and von der Schulenburg JM: A systematic review of the cost-effectiveness of targeted therapies for metastatic non-small cell lung cancer (NSCLC). BMC Pulm Med. 14:1922014. View Article : Google Scholar : PubMed/NCBI
10	Zamora-Ros R, Knaze V, Lujan-Barroso L, Romieu I, Scalbert A, Slimani N, Hjartåker A, Engeset D, Skeie G, Overvad K, et al: Differences in dietary intakes, food sources and determinants of total flavonoids between Mediterranean and non-Mediterranean countries participating in the European prospective investigation into cancer and nutrition (EPIC) study. Br J Nutr. 109:1498–1507. 2013. View Article : Google Scholar : PubMed/NCBI
11	Cheng Y, Tan J, Li H, Kong X, Liu Y, Guo R, Li G, Yang B and Pei M: Cardioprotective effects of total flavonoids from Jinhe Yangxin prescription by activating the PI3K/Akt signaling pathway in myocardial ischemia injury. Biomed Pharmacother. 98:308–317. 2018. View Article : Google Scholar : PubMed/NCBI
12	Zhang XX, Wu QF, Yan YL and Zhang FL: Inhibitory effects and related molecular mechanisms of total flavonoids in Mosla Chinensis Maxim against H1N1 influenza virus. Inflamm Res. 67:179–189. 2018. View Article : Google Scholar : PubMed/NCBI
13	Liu Q, Zhang L, Shan Q, Ding Y, Zhang Z, Zhu M and Mao Y: Total flavonoids from Astragalus alleviate endothelial dysfunction by activating the Akt/eNOS pathway. J Int Med Res. 46:2096–2103. 2018. View Article : Google Scholar : PubMed/NCBI
14	Wang G, Wang J, Du L and Li F: Effect and mechanism of total flavonoids extracted from cotinus coggygria against glioblastoma cancer in vitro and in vivo. Biomed Res Int. 2015:8563492015. View Article : Google Scholar : PubMed/NCBI
15	Du WJ, Yang XL, Song ZJ, Wang JY, Zhang WJ, He X, Zhang RQ, Zhang CF, Li F, Yu CH, et al: Antitumor activity of total flavonoids from daphne genkwa in colorectal cancer. Phytother Res. 30:323–330. 2016. View Article : Google Scholar : PubMed/NCBI
16	Wang Y, Cao HJ, Sun SJ, Dai JY, Fang JW, Li QH, Yan C, Mao WW and Zhang YY: Total flavonoid aglycones extract in Radix scutellariae inhibits lung carcinoma and lung metastasis by affecting cell cycle and DNA synthesis. J Ethnopharmacol. 194:269–279. 2016. View Article : Google Scholar : PubMed/NCBI
17	Xiao S, Wang J and Xiao N: MicroRNAs as noninvasive biomarkers in bladder cancer detection: A diagnostic meta-analysis based on qRT-PCR data. Int J Biol Markers. 31:e276–e285. 2016. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
19	Chen L, Wei Y, Zhao S, Zhang M, Yan X, Gao X, Li J and Gao Y, Zhang A and Gao Y: Antitumor and immunomodulatory activities of total flavonoids extract from persimmon leaves in H22 liver tumor-bearing mice. Sci Rep. 8:105232018. View Article : Google Scholar : PubMed/NCBI
20	Feng Z, Hao W, Lin X, Fan D and Zhou J: Antitumor activity of total flavonoids from Tetrastigma hemsleyanum Diels et Gilg is associated with the inhibition of regulatory T cells in mice. OncoTargets Ther. 7:947–956. 2014.
21	Zhuang T, Djemil T, Qi P, Magnelli A, Stephans K, Videtic G and Xia P: Dose calculation differences between Monte Carlo and pencil beam depend on the tumor locations and volumes for lung stereotactic body radiation therapy. J Appl Clin Med Phys. 14:40112013. View Article : Google Scholar : PubMed/NCBI
22	Stepanichev M, Markov D, Pasikova N and Gulyaeva N: Behavior and the cholinergic parameters in olfactory bulbectomized female rodents: Difference between rats and mice. Behav Brain Res. 297:5–14. 2016. View Article : Google Scholar : PubMed/NCBI
23	Kalyuzhny AE: Combination of TUNEL assay with immunohistochemistry for simultaneous detection of DNA fragmentation and oxidative cell damage. Methods Mol Biol. 682:15–27. 2011. View Article : Google Scholar : PubMed/NCBI
24	Ren Z, Zhou S, Liu Z and Xu S: Randomized controlled trials of induction treatment and surgery versus combined chemotherapy and radiotherapy in stages IIIA-N2 NSCLC: A systematic review and meta-analysis. J Thorac Dis. 7:1414–1422. 2015.PubMed/NCBI
25	Cao X, Zou H, Cao J, Cui Y, Sun S, Ren K, Song Z, Li D and Quan M: A candidate Chinese medicine preparation-fructus viticis total flavonoids inhibits stem-like characteristics of lung cancer stem-like cells. BMC Complement Altern Med. 16:3642016. View Article : Google Scholar : PubMed/NCBI
26	Attoub S, Hassan AH, Vanhoecke B, Iratni R, Takahashi T, Gaben AM, Bracke M, Awad S, John A, Kamalboor HA, et al: Inhibition of cell survival, invasion, tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells. Eur J Pharmacol. 651:18–25. 2011. View Article : Google Scholar : PubMed/NCBI
27	Zhu WB, Xiao N and Liu XJ: Dietary flavonoid tangeretin induces reprogramming of epithelial to mesenchymal transition in prostate cancer cells by targeting the PI3K/Akt/mTOR signaling pathway. Oncol Lett. 15:433–440. 2018.PubMed/NCBI
28	Adhami VM, Syed DN, Khan N and Mukhtar H: Dietary flavonoid fisetin: A novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management. Biochem Pharmacol. 84:1277–1281. 2012. View Article : Google Scholar : PubMed/NCBI
29	He L, Wu Y, Lin L, Wang J, Wu Y, Chen Y, Yi Z, Liu M and Pang X: Hispidulin, a small flavonoid molecule, suppresses the angiogenesis and growth of human pancreatic cancer by targeting vascular endothelial growth factor receptor 2-mediated PI3K/Akt/mTOR signaling pathway. Cancer Sci. 102:219–225. 2011. View Article : Google Scholar : PubMed/NCBI
30	Wang S, Tian Q and An F: Growth inhibition and apoptotic effects of total flavonoids from Trollius chinensis on human breast cancer MCF-7 cells. Oncol Lett. 12:1705–1710. 2016. View Article : Google Scholar : PubMed/NCBI
31	Qinglin L, Xin W, Like Z, Fang L, Cao G and Huang P: A study on the anti-tumor mechanism of total flavonoids from radix tetrastigmae against additional cell line based on COX-2-mediated Wnt/β -catenin signaling pathway. Oncotarget. 8:54304–54319. 2017. View Article : Google Scholar : PubMed/NCBI
32	Schweigert A, Fischer C, Mayr D, von Schweinitz D, Kappler R and Hubertus J: Activation of the Wnt/β-catenin pathway is common in wilms tumor, but rarely through beta-catenin mutation and APC promoter methylation. Pediatr Surg Int. 32:1141–1146. 2016. View Article : Google Scholar : PubMed/NCBI
33	Ye Y, Long X, Zhang L, Chen J, Liu P, Li H, Wei F, Yu W, Ren X and Yu J: NTS/NTR1 co-expression enhances epithelial-to-mesenchymal transition and promotes tumor metastasis by activating the Wnt/β-catenin signaling pathway in hepatocellular carcinoma. Oncotarget. 7:70303–70322. 2016. View Article : Google Scholar : PubMed/NCBI
34	Lin HH, Feng WC, Lu LC, Shao YY, Hsu CH and Cheng AL: Inhibition of the Wnt/beta-catenin signaling pathway improves the anti-tumor effects of sorafenib against hepatocellular carcinoma. Cancer Lett. 381:58–66. 2016. View Article : Google Scholar : PubMed/NCBI
35	Bi X, Xia X, Mou T, Jiang B, Fan D, Wang P, Liu Y, Hou Y and Zhao Y: Anti-tumor activity of three ginsenoside derivatives in lung cancer is associated with Wnt/β-catenin signaling inhibition. Eur J Pharmacol. 742:145–152. 2014. View Article : Google Scholar : PubMed/NCBI