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

An,Qi; Han,Chao; Zhou,Yubing; Li,Feng; Li,Duolu; Zhang,Xiaojian; Yu,Zujiang; Duan,Zhenfeng; Kan,Quancheng

doi:10.3892/mmr.2016.5753

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

Authors:
- Qi An
- Chao Han
- Yubing Zhou
- Feng Li
- Duolu Li
- Xiaojian Zhang
- Zujiang Yu
- Zhenfeng Duan
- Quancheng Kan
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Affiliations: Department of Clinical Pharmacology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, MA 02114, USA
Published online on: September 20, 2016 https://doi.org/10.3892/mmr.2016.5753
Pages: 4042-4048
Copyright: © An et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality in the United States. Chemotherapy prolongs survival rates among patients with advanced disease, however, this is at the cost of clinically significant adverse effects. Matrine is an active component of traditional Chinese medicine and is a promising alternative drug for the treatment of NSCLC. In the present study, the therapeutic effects and the underlying molecular mechanisms of matrine on the A549 NSCLC cell line were investigated. A high concentration of matrine (1.0 mg/ml) significantly (P<0.05) inhibited cell proliferation, by 52.68±3.32%, under which cell shrinkage and disruption were observed. Flow cytometric analysis showed that the proportion of G1/G0 cells was significantly increased, whereas the proportions of S and G2/M cells were significantly decreased (P<0.05) following treatment with matrine for 48 h. These results indicated that cell arrest was induced by matrine. Upregulation of the expression of microRNA (miR)‑126, followed by downregulation of the expression of its target gene, vascular endothelial growth factor, were detected following treatment with a low concentration of matrine (0.2 mg/ml) using reverse transcription‑quantitative polymerase chain reaction analysis, immunohistochemistry and western blot analysis. In conclusion, matrine induced cell cycle arrest and apoptosis, and recovered the expression of miR‑126 in the A549 NSCLC cell line.

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1	Ettinger DS, Akerley W, Borghaei H, Chang AC, Cheney RT, Chirieac LR, D'Amico TA, Demmy TL, Ganti AK, Govindan R, et al: Non-small cell lung cancer. J Natl Compr Canc Netw. 10:1236–1271. 2012.PubMed/NCBI
2	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI
3	Biesalski HK, de Mesquita B Bueno, Chesson A, Chytil F, Grimble R, Hermus RJ, Köhrle J, Lotan R, Norpoth K, Pastorino U and Thurnham D: European consensus statement on lung cancer: Risk factors and prevention. Lung cancer panel. CA Cancer J Clin. 48:167–176; discussion 164–166. 1998. View Article : Google Scholar : PubMed/NCBI
4	Secretan B, Straif K, Baan R, Grosse Y, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, et al: A review of human carcinogens-Part E: Tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol. 10:1033–1034. 2009. View Article : Google Scholar : PubMed/NCBI
5	Martínez-Sánchez JM, Fernández E, Fu M, Gallus S, Martínez C, Sureda X, La Vecchia C and Clancy L: Smoking behaviour, involuntary smoking, attitudes towards smoke-free legislations, and tobacco control activities in the European Union. PLoS One. 5:e138812010. View Article : Google Scholar : PubMed/NCBI
6	Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, Kalman L, Miller V, Lee JS, Moore M, et al: TAX Non-Small-Cell Lung Cancer Study Group: Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. JCO. 18:2354–2362. 2000.
7	Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J and Johnson DH: Eastern Cooperative Oncology Group: Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 346:92–98. 2002. View Article : Google Scholar : PubMed/NCBI
8	Avila MA, Berasain C, Sangro B and Prieto J: New therapies for hepatocellular carcinoma. Oncogene. 25:3866–3884. 2006. View Article : Google Scholar : PubMed/NCBI
9	Llovet JM and Bruix J: Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 37:429–442. 2003. View Article : Google Scholar : PubMed/NCBI
10	Hartmann TN, Burger JA, Glodek A, Fujii N and Burger M: CXCR4 chemokine receptor and integrin signaling co-operate in mediating adhesion and chemoresistance in small cell lung cancer (SCLC) cells. Oncogene. 24:4462–4471. 2005. View Article : Google Scholar : PubMed/NCBI
11	Taron M, Rosell R, Felip E, Mendez P, Souglakos J, Ronco MS, Queralt C, Majo J, Sanchez JM, Sanchez JJ and Maestre J: BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer. Hum Mol Genet. 13:2443–2449. 2004. View Article : Google Scholar : PubMed/NCBI
12	Ma L, Wen S, Zhan Y, He Y, Liu X and Jiang J: Anticancer effects of the Chinese medicine matrine on murine hepatocellular carcinoma cells. Planta Med. 74:245–251. 2008. View Article : Google Scholar : PubMed/NCBI
13	Yan Z, Jikai J, Xiaoshan L, et al: Differentiation and apoptosis in K562 erythroleukemia cells induced by matrine. Natural Med. 52:295–299. 1998.
14	Li CQ, Zhu YT, Zhang FX, Fu LC, Li XH, Cheng Y and Li XY: Anti-HBV effect of liposome-encapsulated matrine in vitro and in vivo. World J Gastroenterol. 11:426–428. 2005. View Article : Google Scholar : PubMed/NCBI
15	Liu J, Zhu M, Shi R and Yang M: Radix Sophorae flavescentis for chronic hepatitis B: A systematic review of randomized trials. Am J Chin Med. 31:337–354. 2003. View Article : Google Scholar : PubMed/NCBI
16	Zhang JP, Zhang M, Zhou JP, Liu FT, Zhou B, Xie WF and Guo C: Antifibrotic effects of matrine on in vitro and in vivo models of liver fibrosis in rats. Acta Pharmacol Sin. 22:183–186. 2001.PubMed/NCBI
17	Zhang LP, Jiang JK, Tam JW, Zhang Y, Liu XS, Xu XR, Liu BZ and He YJ: Effects of matrine on proliferation and differentiation in K-562 cells. Leuk Res. 25:793–800. 2001. View Article : Google Scholar : PubMed/NCBI
18	Zhang YQ, Huang GS, Wang Z, Guo Y and Zhang HY: Effects of matrine on the relative molecules expression of proliferation and apoptosis in K562 cells. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 23:333–336. 2001.(In Chinese). PubMed/NCBI
19	Wang Y, Peng C, Zhang G, Liu Y, Li H and Shan J: Study on invasion and metastasis related factors in differentiation of SMMC-7721 cells induced by matrine. Zhong Yao Cai. 26:566–569. 2003.(In Chinese). PubMed/NCBI
20	Han Y, Zhang S, Wu J, Yu K, Zhang Y, Yin L and Bi L: Matrine induces apoptosis of human multiple myeloma cells via activation of the mitochondrial pathway. Leuk Lymphoma. 51:1337–1346. 2010. View Article : Google Scholar : PubMed/NCBI
21	Luo C, Zhu Y, Jiang T, Lu X, Zhang W, Jing Q, Li J, Pang L, Chen K, Qiu F, et al: Matrine induced gastric cancer MKN45 cells apoptosis via increasing pro-apoptotic molecules of Bcl-2 family. Toxicology. 229:245–252. 2007. View Article : Google Scholar : PubMed/NCBI
22	Zhang L, Wang T, Wen X, Wei Y, Peng X, Li H and Wei L: Effect of matrine on HeLa cell adhesion and migration. Eur J Pharmacol. 563:69–76. 2007. View Article : Google Scholar : PubMed/NCBI
23	Hou G, Li N, Ma Y-H, Chen X-B, Wang X-F and Luo S-X: Expression of Survivin and P-glycoprotein in non-small cell lung cancer and their relationship with the effectiveness of Matrine and pacilitaxel. Chin J Cancer Prev Treat. 20:350–353. 2013.
24	Liu B, Peng XC, Zheng XL, Wang J and Qin YW: MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer. 66:169–175. 2009. View Article : Google Scholar : PubMed/NCBI
25	Janmaat ML, Kruyt FA, Rodriguez JA and Giaccone G: Response to epidermal growth factor receptor inhibitors in non-small cell lung cancer cells: Limited antiproliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways. Clin Cancer Res. 9:2316–2326. 2003.PubMed/NCBI
26	Danielsen T, Hvidsten M, Stokke T, Solberg K and Rofstad EK: Hypoxia induces p53 accumulation in the S-phase and accumulation of hypophosphorylated retinoblastoma protein in all cell cycle phases of human melanoma cells. Br J Cancer. 78:1547–1558. 1998. View Article : Google Scholar : PubMed/NCBI
27	Takeuchi K, Choi YL, Togashi Y, Soda M, Hatano S, Inamura K, Takada S, Ueno T, Yamashita Y, Satoh Y, et al: KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res. 15:3143–3149. 2009. View Article : Google Scholar : PubMed/NCBI
28	Wu P, Dugoua JJ, Eyawo O and Mills EJ: Traditional Chinese medicines in the treatment of hepatocellular cancers: A systematic review and meta-analysis. J Exp Clin Cancer Res. 28:1122009. View Article : Google Scholar : PubMed/NCBI
29	Efferth T, Li PC, Konkimalla VS and Kaina B: From traditional Chinese medicine to rational cancer therapy. Trends Mol Med. 13:353–361. 2007. View Article : Google Scholar : PubMed/NCBI
30	Efferth T, Dunstan H, Sauerbrey A, Miyachi H and Chitambar CR: The anti-malarial artesunate is also active against cancer. Int J Oncol. 18:767–773. 2001.PubMed/NCBI
31	Efferth T, Sauerbrey A, Olbrich A, Gebhart E, Rauch P, Weber HO, Hengstler JG, Halatsch ME, Volm M, Tew KD, et al: Molecular modes of action of artesunate in tumor cell lines. Mol Pharmacol. 64:382–394. 2003. View Article : Google Scholar : PubMed/NCBI
32	Ooi LS, Wang H, Luk CW and Ooi VE: Anticancer and antiviral activities of Youngia japonica (L.) DC (Asteraceae, Compositae). J Ethnopharmacol. 94:117–122. 2004. View Article : Google Scholar : PubMed/NCBI