Nifedipine stimulates proliferation and migration of different breast cancer cells by distinct pathways

Zhao,Tao; Guo,Dongqing; Gu,Yuchun; Ling,Yang

doi:10.3892/mmr.2017.6818

Nifedipine stimulates proliferation and migration of different breast cancer cells by distinct pathways

Authors:
- Tao Zhao
- Dongqing Guo
- Yuchun Gu
- Yang Ling
View Affiliations

Affiliations: Changzhou Tumor Hospital Affiliated of Suzhou University, Changzhou, Jiangsu 213000, P.R. China, School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, P.R. China, Laboratory of Molecular Pharmacology, Institute of Molecular Medicine, Peking University, Beijing 100871, P.R. China
Published online on: June 20, 2017 https://doi.org/10.3892/mmr.2017.6818
Pages: 2259-2263

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

Nifedipine is widely used to treat high blood pressure and angina. Were nifedipine able to promote the proliferation and migration of breast cancer, it would pose a significant threat for patients. Thus, it is important to determine the effects of nifedipine on breast cancer and the mechanism involved. The present study identified that nifedipine significantly promoted the proliferation and migration of breast cancer cells in vitro. The mechanism of nifedipine on different breast cancer cells was investigated and it was identified that the effects of nifedipine on MCF‑7 cells were via the protein kinase B‑endothelial constitutive nitric oxide synthase‑nitric oxide axis, and on MDA‑MB‑231 cells via activation of the extracellular signal‑regulated kinase pathway. These results identified the distinct pathways in the activation of cell proliferation and migration presented in different cell lines by nifedipine. The present study advises that nifedipine can promote breast cancer and should be avoided for women who suffer from breast cancer and hypertension.

View Figures

View References

1	Needleman H and Huff J: The international agency for research on cancer and obligate transparency. Lancet Oncol. 6:920–921. 2005. View Article : Google Scholar : PubMed/NCBI
2	Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, van Tine BA, Hoog J, Goiffon RJ, Goldstein TC, et al: Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature. 486:353–360. 2012.PubMed/NCBI
3	Ruark E, Snape K, Humburg P, Loveday C, Bajrami I, Brough R, Rodrigues DN, Renwick A, Seal S, Ramsay E, et al: Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer. Nature. 493:406–410. 2013. View Article : Google Scholar : PubMed/NCBI
4	Stephens PJ, Tarpey PS, Davies H, van Loo P, Greenman C, Wedge DC, Nik-Zainal S, Martin S, Varela I, Bignell GR, et al: The landscape of cancer genes and mutational processes in breast cancer. Nature. 486:400–404. 2012.PubMed/NCBI
5	Li W, Shi Q, Wang W, Liu J, Li Q and Hou F: Calcium channel blockers and risk of breast cancer: A meta-analysis of 17 observational studies. PLoS One. 9:e1058012014. View Article : Google Scholar : PubMed/NCBI
6	Li CI, Malone KE, Weiss NS, Boudreau DM, Cushing-Haugen KL and Daling JR: Relation between use of antihypertensive medications and risk of breast carcinoma among women ages 65–79 years. Cancer. 98:1504–1513. 2003. View Article : Google Scholar : PubMed/NCBI
7	Largent JA, Bernstein L, Horn-Ross PL, Marshall SF, Neuhausen S, Reynolds P, Ursin G, Zell JA, Ziogas A and Anton-Culver H: Hypertension, antihypertensive medication use, and breast cancer risk in the California teachers study cohort. Cancer Causes Control. 21:1615–1624. 2010. View Article : Google Scholar : PubMed/NCBI
8	Guo DQ, Zhang H, Tan SJ and Gu YC: Nifedipine promotes the proliferation and migration of breast cancer cells. PLoS One. 9:e1136492014. View Article : Google Scholar : PubMed/NCBI
9	Ahr HJ, Bomhard E, Enzmann H, Karbe E, Mager H, Sander E and Schlüter G: Calcium channel blockers and the risk of cancer: A preclinical assessment. Cardiovasc Drugs Ther. 12:157–169. 1998. View Article : Google Scholar : PubMed/NCBI
10	Braun S, Boyko V, Behar S, Reicher-Reiss H, Laniado S, Kaplinsky E and Goldbourt U: Calcium channel blocking agents and risk of cancer in patients with coronary heart disease. Benzafibrate infarction prevention (BIP) study research group. J Am Coll Cardiol. 31:804–808. 1998. View Article : Google Scholar : PubMed/NCBI
11	Fryzek JP, Poulsen AH, Lipworth L, Pedersen L, Nørgaard M, McLaughlin JK and Friis S: A cohort study of antihypertensive medication use and breast cancer among Danish women. Breast Cancer Res Treat. 97:231–236. 2006. View Article : Google Scholar : PubMed/NCBI
12	Coleman CI, Baker WL, Kluger J and White CM: Antihypertensive medication and their impact on cancer incidence: A mixed treatment comparison meta-analysis of randomized controlled trials. J Hypertens. 26:622–629. 2008. View Article : Google Scholar : PubMed/NCBI
13	Alfonzo-Méndez MA, Castillo-Badillo JA, Romero-Ávila MT, Rivera R, Chun J and García-Sáinz JA: Carboxyl terminus-truncated alpha1D-adrenoceptors inhibit the ERK pathway. Naunyn Schmiedebergs Arch Pharmacol. 389:911–920. 2016. View Article : Google Scholar : PubMed/NCBI
14	Soule HD, Vazguez J, Long A, Albert S and Brennan M: A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst. 51:1409–1416. 1973. View Article : Google Scholar : PubMed/NCBI
15	Tabei I, Nishiyama S, Yamashita S, Hashimoto H, Tachibana T, Uchida K and Ishikawa H: Establishment and characterization of HER2-positive cell line derived from pleural effusion of human breast scirrhous carcinoma Hum. Cell. 21:105–112. 2008.
16	Cailleau R, Young R, Olivé M and Reeves WJ Jr: Breast tumor cell lines from pleural effusions. J Natl Cancer Inst. 53:661–674. 1974. View Article : Google Scholar : PubMed/NCBI
17	Zhang Y, Gupta A, Wang H, Zhou L, Vethanayagam RR, Unadkat JD and Mao Q: BCRP transports dipyridamole and is inhibited by calcium channel blockers. Pharm Res. 22:2023–2034. 2005. View Article : Google Scholar : PubMed/NCBI
18	Timcheva CV and Todorov DK: Does verapamil help overcome multidrug resistance in tumor cell lines and cancer patients? J Chemother. 8:295–299. 1996. View Article : Google Scholar : PubMed/NCBI
19	Correale P, Tagliaferri P, Celio L, Genua G, Montagnani S and Bianco AR: Verapamil upregulates sensitivity of human colon and breast cancer cells to LAK-cytotoxicity in vitro. Eur J Cancer. 27:1393–1395. 1991. View Article : Google Scholar : PubMed/NCBI
20	Fine RL, Patel J and Chabner BA: Phorbol esters induce multidrug resistance in human breast cancer cells. Proc Natl Acad Sci USA. 85:582–586. 1988. View Article : Google Scholar : PubMed/NCBI
21	Garcia-Fernandez MO, Schally AV, Varga JL, Groot K and Busto R: The expression of growth hormone-releasing hormone (GHRH) and its receptor splice variants in human breast cancer lines; the evaluation of signaling mechanisms in the stimulation of cell proliferation. Breast Cancer Res Treat. 77:15–26. 2003. View Article : Google Scholar : PubMed/NCBI
22	Nie L, Oishi Y, Doi I, Shibata H and Kojima I: Inhibition of proliferation of MCF-7 breast cancer cells by a blocker of Ca(2+)-permeable channel. Cell Calcium. 22:75–82. 1997. View Article : Google Scholar : PubMed/NCBI
23	Chung SY, Sung MK, Kim NH, Jang JO, Go EJ and Lee HJ: Inhibition of P-glycoprotein by natural products in human breast cancer cells. Arch Pharm Res. 28:823–828. 2005. View Article : Google Scholar : PubMed/NCBI
24	Zhou XF, Yang X, Wang Q, Coburn RA and Morris ME: Effects of dihydropyridines and pyridines on multidrug resistance mediated by breast cancer resistance protein: In vitro and in vivo studies. Drug Metab Dispos. 33:1220–1228. 2005. View Article : Google Scholar : PubMed/NCBI
25	Roger S, Le Guennec JY and Besson P: Particular sensitivity to calcium channel blockers of the fast inward voltage-dependent sodium current involved in the invasive properties of a metastastic breast cancer cell line. Br J Pharmacol. 141:610–615. 2004. View Article : Google Scholar : PubMed/NCBI
26	Loibl S, Bratengeier J, Farines V, von Minckwitz G, Spänkuch B, Schini-Kerth V, Nepveu F, Strebhardt K and Kaufmann M: Investigations on the inducible and endothelial nitric oxide synthases in human breast cancer cell line MCF-7-estrogen has an influence on e-NOS, but not on i-NOS. Pathol Res Pract. 202:1–7. 2006. View Article : Google Scholar : PubMed/NCBI
27	Cheng RY, Basudhar D, Ridnour LA, Heinecke JL, Kesarwala AH, Glynn S, Switzer CH, Ambs S, Miranda KM and Wink DA: Gene expression profiles of NO- and HNO-donor treated breast cancer cells: Insights into tumor response and resistance pathways. Nitric Oxide. 43:17–28. 2014. View Article : Google Scholar : PubMed/NCBI