Pectolinarigenin inhibits non‑small cell lung cancer progression  by regulating the PTEN/PI3K/AKT signaling pathway

Xu,Fei; Gao,Xuan; Pan,Huiyun

doi:10.3892/or.2018.6759

Pectolinarigenin inhibits non‑small cell lung cancer progression by regulating the PTEN/PI3K/AKT signaling pathway

Authors:
- Fei Xu
- Xuan Gao
- Huiyun Pan
View Affiliations

Affiliations: Department of Internal Medicine Ward, The First Affiliated Hospital of the College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Department of Respiratory Diseases, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China
Published online on: October 2, 2018 https://doi.org/10.3892/or.2018.6759
Pages: 3458-3468
Copyright: © Xu 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

Lung cancer is the principal cause of cancer‑associated mortality. Pectolinarigenin (Pec) reportedly has effective antitumor activity against certain cancer types. Phosphatase and tensin homolog (PTEN) is a well‑known tumor suppressor and serves a vital role in cancer progression. However, the effect of Pec on non‑small cell lung cancer (NSCLC) cell proliferation and metastasis, and the underlying mechanism, has not yet been elucidated. In the present study, it was demonstrated that Pec inhibited the proliferation of A549 and Calu‑3 cells in dose‑ and time‑dependent manners. The apoptosis rate significantly increased with increasing doses of Pec. Apoptosis‑associated protein expression was additionally altered by Pec exposure. Pec was able to suppress the metastasis of NSCLC cells; it upregulated the mRNA and protein expression levels of E‑cadherin, and downregulated the mRNA and protein expression levels of vimentin. Additionally, Pec was able to activate PTEN and subsequently downregulate the PI3K/protein kinase B (AKT) signaling pathway. In summary, Pec was able to inhibit cell proliferation, promote apoptosis and suppress metastasis in NSCLC cells through the PTEN/PI3K/AKT signaling pathway, indicating that Pec is a potential agent for NSCLC therapy.

View Figures

View References

1	Smith RA, Andrews KS, Brooks D, Fedewa SA, Manassaram-Baptiste D, Saslow D, Brawley OW and Wender RC: Cancer screening in the United States, 2017: A review of current american cancer society guidelines and current issues in cancer screening. CA Cancer J Clin. 67:100–121. 2017. View Article : Google Scholar : PubMed/NCBI
2	By the numbers: Cancer mortality, 2011–2015. Cancer Discov. 8:9072018.
3	de Groot PM, Wu CC, Carter BW and Munden RF: The epidemiology of lung cancer. Transl Lung Cancer Res. 7:220–233. 2018. View Article : Google Scholar : PubMed/NCBI
4	Rybarczyk-Kasiuchnicz A and Ramlau R: Current views on molecularly targeted therapy for lung cancer-a review of literature from the last five years. Kardiochir Torakochirurgia Pol. 15:119–124. 2018.PubMed/NCBI
5	Varol M, Koparal AT, Benkli K and Bostancioglu RB: Anti-lung cancer and anti-angiogenic activities of new designed boronated phenylalanine metal complexes. Curr Drug Deliv. Jul 27–2018.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
6	Miura Y and Sunaga N: Role of immunotherapy for oncogene-driven non-small cell lung cancer. Cancers (Basel). 10:E2452018. View Article : Google Scholar : PubMed/NCBI
7	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
8	Chen CY, Chen J, He L and Stiles BL: PTEN: Tumor suppressor and metabolic regulator. Front Endocrinol (Lausanne). 9:3382010. View Article : Google Scholar
9	Jamaspishvili T, Berman DM, Ross AE, Scher HI, De Marzo AM, Squire JA and Lotan TL: Clinical implications of PTEN loss in prostate cancer. Nat Rev Urol. 15:222–234. 2018. View Article : Google Scholar : PubMed/NCBI
10	Lee YR, Chen M and Pandolfi PP: The functions and regulation of the PTEN tumour suppressor: New modes and prospects. Nat Rev Mol Cell Biol. 19:547–562. 2018. View Article : Google Scholar : PubMed/NCBI
11	Kong Y, Yin J, Fu Y, Chen Y, Zhou Y and Geng X: Suppression of Elk1 inhibits thyroid cancer progression by mediating PTEN expression. Oncol Rep. 40:1769–1776. 2018.PubMed/NCBI
12	Tian DD, Zhang RX, Wu N, Yuan W, Luo SH, Chen HQ, Liu Y, Wang Y, He BC and Deng ZL: Tetrandrine inhibits the proliferation of human osteosarcoma cells by upregulating the PTEN pathway. Oncol Rep. 37:2795–2802. 2017. View Article : Google Scholar : PubMed/NCBI
13	Xiong J, Li Z, Zhang Y, Li D, Zhang G, Luo X, Jie Z, Liu Y, Cao Y, Le Z, et al: PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN. Oncol Rep. 36:1819–1828. 2016. View Article : Google Scholar : PubMed/NCBI
14	Zhang J, Yang C, Zhou F and Chen X: PDK1 inhibitor GSK2334470 synergizes with proteasome inhibitor MG132 in multiple myeloma cells by inhibiting full AKT activity and increasing nuclear accumulation of the PTEN protein. Oncol Rep. 39:2951–2959. 2018.PubMed/NCBI
15	Zhao Y, Zheng R, Li J, Lin F and Liu L: Loss of phosphatase and tensin homolog expression correlates with clinicopathological features of non-small cell lung cancer patients and its impact on survival: A systematic review and meta-analysis. Thorac Cancer. 8:203–213. 2017. View Article : Google Scholar : PubMed/NCBI
16	Zhu X, Li Z, Li T, Long F, Lv Y, Liu L, Liu X and Zhan Q: Osthole inhibits the PI3K/AKT signaling pathway via activation of PTEN and induces cell cycle arrest and apoptosis in esophageal squamous cell carcinoma. Biomed Pharmacother. 102:502–509. 2018. View Article : Google Scholar : PubMed/NCBI
17	Lim SL, Goh YM, Noordin MM, Rahman HS, Othman HH, Bakar Abu NA and Mohamed S: Morinda citrifolia edible leaf extract enhanced immune response against lung cancer. Food Funct. 7:741–751. 2016. View Article : Google Scholar : PubMed/NCBI
18	Wang C, Cheng Y, Liu H, Xu Y, Peng H, Lang J, Liao J, Liu H, Liu H and Fan J: Pectolinarigenin suppresses the tumor growth in nasopharyngeal carcinoma. Cell Physiol Biochem. 39:1795–1803. 2016. View Article : Google Scholar : PubMed/NCBI
19	Zhang T, Li S, Li J, Yin F, Hua Y, Wang Z, Lin B, Wang H, Zou D, Zhou Z, et al: Natural product pectolinarigenin inhibits osteosarcoma growth and metastasis via SHP-1-mediated STAT3 signaling inhibition. Cell Death Dis. 7:e24212016. View Article : Google Scholar : PubMed/NCBI
20	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
21	Lu C, Wang H, Chen S, Yang R, Li H and Zhang G: Baicalein inhibits cell growth and increases cisplatin sensitivity of A549 and H460 cells via miR-424-3p and targeting PTEN/PI3K/Akt pathway. J Cell Mol Med. 22:2478–2487. 2018. View Article : Google Scholar : PubMed/NCBI
22	Yu C, Zhang B, Li YL and Yu XR: SIX1 reduces the expression of PTEN via activating PI3K/AKT signal to promote cell proliferation and tumorigenesis in osteosarcoma. Biomed Pharmacother. 105:10–17. 2018. View Article : Google Scholar : PubMed/NCBI
23	Li Z, Hong S and Liu Z: LncRNA LINC00641 predicts prognosis and inhibits bladder cancer progression through miR-197-3p/KLF10/PTEN/PI3K/AKT cascade. Biochem Biophys Res Commun. 503:1825–1829. 2018. View Article : Google Scholar : PubMed/NCBI
24	Liu J, Xing Y and Rong L: miR-181 regulates cisplatin-resistant non-small cell lung cancer via downregulation of autophagy through the PTEN/PI3K/AKT pathway. Oncol Rep. 39:1631–1639. 2018.PubMed/NCBI
25	Jing X, Cheng W, Wang S, Li P and He L: Resveratrol induces cell cycle arrest in human gastric cancer MGC803 cells via the PTEN-regulated PI3K/Akt signaling pathway. Oncol Rep. 35:472–478. 2016. View Article : Google Scholar : PubMed/NCBI
26	Matsuda S, Nakagawa Y, Kitagishi Y, Nakanishi A and Murai T: Reactive oxygen species, superoxide dimutases, and PTEN-p53-AKT-MDM2 signaling loop network in mesenchymal stem/stromal cells regulation. Cells. 7:E362018. View Article : Google Scholar : PubMed/NCBI
27	de Assis LV and Isoldi MC: The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: A review focused on the genes' molecular mechanisms. Tumour Biol. 35:889–901. 2014. View Article : Google Scholar : PubMed/NCBI
28	He M, Jiang L, Li B, Wang G, Wang J and Fu Y: Oxymatrine suppresses the growth and invasion of MG63 cells by up-regulating PTEN and promoting its nuclear translocation. Oncotarget. 8:65100–65110. 2017.PubMed/NCBI
29	Oxnard GR, Hu Y, Mileham KF, Husain H, Costa DB, Tracy P, Feeney N, Sholl LM, Dahlberg SE, Redig AJ, et al: Assessment of resistance mechanisms and clinical implications in patients with EGFR T790m-positive lung cancer and acquired resistance to osimertinib. JAMA Oncol. Aug 2–2018.(Epub ahead of print). View Article : Google Scholar
30	Dai Z, Wang L, Wang X, Zhao B, Zhao W, Bhardwaj SS, Ye J, Yin Z, Zhang J and Zhao S: Oxymatrine induces cell cycle arrest and apoptosis and suppresses the invasion of human glioblastoma cells through the EGFR/PI3K/Akt/mTOR signaling pathway and STAT3. Oncol Rep. 40:867–876. 2018.PubMed/NCBI
31	Li W, Yu X, Ma X, Xie L, Xia Z, Liu L, Yu X, Wang J, Zhou H, Zhou X, et al: Deguelin attenuates non-small cell lung cancer cell metastasis through inhibiting the CtsZ/FAK signaling pathway. Cell Signal. 50:131–141. 2018. View Article : Google Scholar : PubMed/NCBI
32	Koundouros N and Poulogiannis G: Phosphoinositide 3-kinase/Akt signaling and redox metabolism in cancer. Front Oncol. 8:1602018. View Article : Google Scholar : PubMed/NCBI
33	Liao K, Yong CW and Hua K: SB431542 inhibited cigarette smoke extract induced invasiveness of A549 cells via the TGF-β1/Smad2/MMP3 pathway. Oncol Lett. 15:9681–9686. 2018.PubMed/NCBI
34	Wu C, Zhu X, Liu W, Ruan T, Wan W and Tao K: NFIB promotes cell growth, aggressiveness, metastasis and EMT of gastric cancer through the Akt/Stat3 signaling pathway. Oncol Rep. 40:1565–1573. 2018.PubMed/NCBI
35	Xing Y, Liu Y, Liu T, Meng Q, Lu H, Liu W, Hu J, Li C, Cao M, Yan S, et al: TNFAIP8 promotes the proliferation and cisplatin chemoresistance of non-small cell lung cancer through MDM2/p53 pathway. Cell Commun Signal. 16:432018. View Article : Google Scholar : PubMed/NCBI