Downregulated miR‑21 mediates matrine‑induced apoptosis via the PTEN/Akt signaling pathway in FTC‑133 human follicular thyroid cancer cells

Li,Quanliang; Zhang,Shuya; Wang,Mingyu; Dong,Shouguang; Wang,Yan; Liu,Song; Lu,Tiancheng; Fu,Yuqin; Wang,Xiuran; Chen,Guihong

doi:10.3892/ol.2019.10693

Downregulated miR‑21 mediates matrine‑induced apoptosis via the PTEN/Akt signaling pathway in FTC‑133 human follicular thyroid cancer cells

Authors:
- Quanliang Li
- Shuya Zhang
- Mingyu Wang
- Shouguang Dong
- Yan Wang
- Song Liu
- Tiancheng Lu
- Yuqin Fu
- Xiuran Wang
- Guihong Chen
View Affiliations

Affiliations: Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, College of Life Sciences, Jilin Agricultural University, Changchun, Jilin 130118, P.R. China, Jilin Hongwuwei BioTech Company, Ji'an, Jilin 134200, P.R. China
Published online on: July 31, 2019 https://doi.org/10.3892/ol.2019.10693
Pages: 3553-3560
Copyright: © Li 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

Matrine is an alkaloid extracted from the leguminous plant Sophora flavescens. Matrine has clinical effects in the treatment of tumors, including those in lung cancer, nasopharyngeal cancer and liver cancer. However, the effect of matrine on follicular thyroid cancer has not been reported. The aim of the present study was to investigate the effect of matrine on follicular thyroid cancer and its potential mechanism. FTC‑133 follicular thyroid cancer cells were treated with different concentrations of matrine, and an MTT assay showed that matrine inhibited the growth of FTC‑133 cells in a dose‑ and time‑dependent manner with an IC50 value of 154.8 µM. Cell apoptosis was analyzed by flow cytometry and the results showed that matrine effectively induced the apoptosis of FTC‑133 cells. The expression level of microRNA (miR)‑21 was analyzed by reverse transcription‑quantitative PCR (RT‑qPCR) analysis, and the mRNA and protein expression levels of PTEN, Akt and phosphorylated (p)‑Akt were detected by RT‑qPCR analysis and western blotting, respectively. The expression of miR‑21 was significantly downregulated, PTEN was upregulated at the mRNA and protein expression levels, and p‑Akt was downregulated in the FTC‑133 cells. The effects of miR‑21 mimics and miR‑21 inhibitor on the expression of miR‑21, PTEN and Akt in FTC‑133 cells, and the effect of miR‑21 mimics/matrine on the expression of PTEN were also investigated. The results of the present study suggested that matrine inhibited the growth and induced apoptosis of FTC‑133 cells via the miR‑21/PTEN/Akt signaling pathway.

View Figures

View References

1	Carling T and Udelsman R: Thyroid cancer. Annu Rev Med. 65:125–137. 2014. View Article : Google Scholar : PubMed/NCBI
2	Li X, Abdel-Mageed AB, Mondal D and Kandil E: MicroRNA expression profiles in differentiated thyroid cancer, a review. Int J Clin Exp Med. 6:74–80. 2013.PubMed/NCBI
3	Jang EK, Song DE, Sim SY, Kwon H, Choi YM, Jeon MJ, Han JM, Kim WG, Kim TY, Shong YK and Kim WB: NRAS codon 61 mutation is associated with distant metastasis in patients with follicular thyroid carcinoma. Thyroid. 24:1275–1281. 2014. View Article : Google Scholar : PubMed/NCBI
4	Schlumberger MJ: Papillary and follicular thyroid carcinoma. N Engl J Med. 338:297–306. 1998. View Article : Google Scholar : PubMed/NCBI
5	Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, et al: 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 26:1–33. 2016. View Article : Google Scholar : PubMed/NCBI
6	Jin H, Sun Y, Wang SY and Cheng XD: Matrine activates PTEN to induce growth inhibition and apoptosis in V600EBRAF harboring melanoma cells. Int J Mol Sci. 14:16040–16057. 2013. View Article : Google Scholar : PubMed/NCBI
7	Wei YP, Wang XH, Liu G, Zhang JF, Yang YX, Zhang J, Song XL, Li ZD and Zhao LD: Matrine exerts inhibitory effects in melanoma through the regulation of miR-19b-3p/PTEN. Int J Oncol. 53:791–800. 2018.PubMed/NCBI
8	Niu HY, Zhang YF, Wu BG, Zhang Y, Jiang HF and He P: Matrine induces the apoptosis of lung cancer cells through downregulation of inhibitor of apoptosis proteins and the Akt signaling pathway. Oncol Rep. 32:1087–1093. 2014. View Article : Google Scholar : PubMed/NCBI
9	An Q, Han C, Zhou Y, Li F, Li D, Zhang X, Yu Z, Duan Z and Kan Q: Matrine induces cell cycle arrest and apoptosis with recovery of the expression of miR-126 in the A549 non-small cell lung cancer cell line. Mol Med Rep. 14:4042–4048. 2016. View Article : Google Scholar : PubMed/NCBI
10	Huang H, Du T, Xu G, Lai Y, Fan XX, Chen X, Li WJ, Yue F, Li Q, Liu L and Li K: Matrine suppresses invasion of castration-resistant prostate cancer cells by downregulating MMP-2/9 via NF-κB signaling pathway. Int J Radiat Oncol. 50:640–648. 2017.
11	Zhao L, Zhang X and Cui S: Matrine inhibits TPC-1 human thyroid cancer cells via the miR-21/PTEN/Akt pathway. Oncol Lett. 16:2965–2970. 2018.PubMed/NCBI
12	Li LQ, Li XL, Wang L, Du WJ, Guo R, Liang HH, Liu X, Liang DS, Lu YJ, Shan HL and Jiang HC: Matrine inhibits breast cancer growth via miR-21/PTEN/Akt pathway in MCF-7 cells. Cell Physiol Biochem. 30:631–641. 2012. View Article : Google Scholar : PubMed/NCBI
13	Tetik Vardarlı A, Düzgün Z, Erdem C, Kaymaz BT, Eroglu Z and Çetintas VB: Matrine induced G0/G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia (T-ALL) cells. Bosn J Basic Med Sci. 18:141–149. 2018.PubMed/NCBI
14	Zhang JG, Wang JJ, Zhao F, Liu Q, Jiang K and Yang GH: MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). Clin Chim Acta. 411:846–852. 2010. View Article : Google Scholar : PubMed/NCBI
15	Moriyama T, Ohuchida K, Mizumoto K, Yu J, Sato N, Nabae T, Takahata S, Toma H, Nagai E and Tanaka M: MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance. Mol Cancer Ther. 8:1067–1074. 2009. View Article : Google Scholar : PubMed/NCBI
16	Fragni M, Bonini SA, Bettinsoli P, Bodei S, Generali D, Bottini A, Spano PF, Memo M and Sigala S: The miR-21/PTEN/Akt signaling pathway is involved in the anti-tumoral effects of zoledronic acid in human breast cancer cell lines. Naunyn Schmiedebergs Arch Pharmacol. 389:529–538. 2016. View Article : Google Scholar : PubMed/NCBI
17	Liu Z, Wang J, Guo C and Fan X: microRNA-21 mediates epithelial-mesenchymal transition of human hepatocytes via PTEN/Akt pathway. Biomed Pharmacother. 69:24–28. 2015. 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	Pfeffer SR, Yang CH and Pfeffer LM: The Role of miR-21 in cancer. Drug Dev Res. 76:270–277. 2015. View Article : Google Scholar : PubMed/NCBI
20	Yang Y, Peng W, Tang T, Xia L, Wang XD, Duan BF and Shu Y: MicroRNAs as promising biomarkers for tumor-staging: Evaluation of MiR21 MiR155 MiR29a and MiR92a in predicting tumor stage of rectal cancer. Asian Pac J Cancer Prev. 15:5175–5180. 2014. View Article : Google Scholar : PubMed/NCBI
21	Bleau AM, Hambardzumyan D, Ozawa T, Fomchenko EI, Huse JT, Brennan CW and Holland EC: PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell. 4:226–235. 2009. View Article : Google Scholar : PubMed/NCBI
22	Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C and González-Barón M: PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 30:193–204. 2004. View Article : Google Scholar : PubMed/NCBI
23	Carnero A, Blanco-Aparicio C, Renner O, Link W and Lea JF: The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets. 8:187–198. 2008. View Article : Google Scholar : PubMed/NCBI
24	Löffler D, Brocke-Heidrich K, Pfeifer G, Stocsits C, Hackermüller J, Kretzschmar AK, Burger R, Gramatzki M, Blumert C, Bauer K, et al: Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood. 110:1330–1333. 2007. View Article : Google Scholar : PubMed/NCBI
25	Yang N, Han F, Cui H, Huang J, Wang T, Zhou Y and Zhou J: Matrine suppresses proliferation and induces apoptosis in human cholangiocarcinoma cells through suppression of JAK2/STAT3 signaling. Pharmacol Rep. 67:388–393. 2015. View Article : Google Scholar : PubMed/NCBI
26	Chen SF, Zhang ZY and Zhang JL: Matrine increases the inhibitory effects of afatinib on H1975 cells via the IL-6/JAK1/STAT3 signaling pathway. Mol Med Rep. 16:2733–2739. 2017. View Article : Google Scholar : PubMed/NCBI