Interference of Notch 1 inhibits the proliferation and invasion of breast cancer cells: Involvement of the β‑catenin signaling pathway

Lai,Xi  Xi; Li,Gang; Lin,Baochai; Yang,Han

doi:10.3892/mmr.2017.8161

Interference of Notch 1 inhibits the proliferation and invasion of breast cancer cells: Involvement of the β‑catenin signaling pathway

Authors:
- Xi Xi Lai
- Gang Li
- Baochai Lin
- Han Yang
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Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Radiation Oncology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: November 27, 2017 https://doi.org/10.3892/mmr.2017.8161
Pages: 2472-2478

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Abstract

Breast cancer is one of the most common types of carcinoma in humans. The aim of the present study was to identify the role of Notch 1 in the proliferation and invasion of human breast cancer cells. Firstly, the levels of Notch 1 were determined by western blot analysis in breast cancer cell lines, and the results revealed that the expression levels of Notch 1 were markedly higher in MDA‑MB‑231 and MCF‑7 cells, and lower in MCF‑10A cells, compared with human mammary epithelial cells. An MTT assay was used to determine the viability of breast cancer cells. The optical density (OD)490 values were significantly decreased in Notch 1 short hairpin (sh)RNA‑transfected MCF‑7 and MDA‑MB‑231 cells, compared with the OD490 values in the negative control shRNA‑transfected cells. The MCF‑7 cells and MDA‑MB‑231 cells were also treated with increasing concentrations of MRK003, a Notch 1 inhibitor, for 24, 48 and 72 h, respectively. The inhibition rate was gradually increased in the MRK003‑treated cells in a time‑ and dose‑dependent manner. The invasive ability of the cells was determined using a Transwell migration assay. The migration ability was significantly decreased in the Notch 1‑transfected MCF‑7 cells and MDA‑MB‑231 cells. The molecular mechanism was examined, and the knockdown of Notch 1 significantly decreased the expression levels of β‑catenin, matrix metalloproteinase (MMP)‑2 and MMP‑9, and was also correlated with the downregulation of β‑catenin in the nucleus. In conclusion, Notch 1 was key in the progression of breast cancer, and knocking down the expression of Notch 1 significantly suppressed the proliferation and invasion of breast cancer cells. This provides novel clues for cancer therapy in human breast cancer.

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1	Wang Y, Yu J, Cui R, Lin J and Ding X: Curcumin in treating breast cancer: A review. J Lab Autom. 21:723–731. 2016. View Article : Google Scholar : PubMed/NCBI
2	Asif HM, Sultana S, Ahmed S, Akhtar N and Tariq M: HER-2 positive breast cancer - a mini-review. Asian Pac J Cancer Prev. 17:1609–1615. 2016. View Article : Google Scholar : PubMed/NCBI
3	Zhu L, Li L, Li Y, Wang J and Wang Q: Chinese herbal medicine as an adjunctive therapy for breast cancer: A systematic review and meta-analysis. Evid Based Complement Alternat Med. 2016:94692762016. View Article : Google Scholar : PubMed/NCBI
4	George BP and Abrahamse H: A review on novel breast cancer therapies: Photodynamic therapy and plant derived agent induced cell death mechanisms. Anticancer Agents Med Chem. 16:793–801. 2016. View Article : Google Scholar : PubMed/NCBI
5	Nicolini A, Carpi A, Ferrari P, Biava PM and Rossi G: Immunotherapy and hormone-therapy in metastatic breast cancer: A review and an update. Curr Drug Targets. 17:1127–1139. 2016. View Article : Google Scholar : PubMed/NCBI
6	van Nijnatten TJ, Schipper RJ, Lobbes MB, Nelemans PJ, Beets-Tan RG and Smidt ML: The diagnostic performance of sentinel lymph node biopsy in pathologically confirmed node positive breast cancer patients after neoadjuvant systemic therapy: A systematic review and meta-analysis. Eur J Surg Oncol. 41:1278–1287. 2015. View Article : Google Scholar : PubMed/NCBI
7	Bertozzi S, Londero AP, Cedolini C, Uzzau A, Seriau L, Bernardi S, Bacchetti S, Pasqual EM and Risaliti A: Prevalence, risk factors, and prognosis of peritoneal metastasis from breast cancer. Springerplus. 4:6882015. View Article : Google Scholar : PubMed/NCBI
8	Petekkaya I, Ayyildiz V, Kizilarslanoglu MC, Sahin U, Gezgen G, Roach EC, Karcaaltincaba M and Altundag K: Prognosis of breast cancer in patients with peritoneal metastasis. Breast. 21:420–421. 2012. View Article : Google Scholar : PubMed/NCBI
9	Yasuoka H, Tsujimoto M, Yoshidome K, Nakahara M, Kodama R, Sanke T and Nakamura Y: Cytoplasmic CXCR4 expression in breast cancer: Induction by nitric oxide and correlation with lymph node metastasis and poor prognosis. BMC Cancer. 8:3402008. View Article : Google Scholar : PubMed/NCBI
10	Wu MQ, Hu P, Gao J, Wei WD, Xiao XS, Tang HL, Li X, Ge QD, Jia WH, Liu RB and Xie XM: Low expression of tyrosine-protein phosphatase nonreceptor type 12 is associated with lymph node metastasis and poor prognosis in operable triple-negative breast cancer. Asian Pac J Cancer Prev. 14:287–292. 2013. View Article : Google Scholar : PubMed/NCBI
11	Venkitaraman R, Joseph T, Dhadda A, Chaturvedi A and Upadhyay S: Prognosis of patients with triple-negative breast cancer and brain metastasis. Clin Oncol (R Coll Radiol). 21:729–730. 2009. View Article : Google Scholar : PubMed/NCBI
12	Wikman H, Westphal L, Schmid F, Pollari S, Kropidlowski J, Sielaff-Frimpong B, Glatzel M, Matschke J, Westphal M, Iljin K, et al: Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients. Oncotarget. 5:3076–3087. 2014. View Article : Google Scholar : PubMed/NCBI
13	Yamamura J, Masuda N, Yasojima H, Mizutani M, Kuriyama K, Nakamori S, Sekimoto M, Mano M, Tanaka E and Nonaka M: Clinicopathological factors related to the prognosis of metastatic breast cancer patients after development of brain metastasis. Breast Care (Basel). 10:387–392. 2015. View Article : Google Scholar : PubMed/NCBI
14	Li Y, Jin K, van Pelt GW, van Dam H, Yu X, Mesker WE, Ten Dijke P, Zhou F and Zhang L: c-Myb enhances breast cancer invasion and metastasis through the Wnt/β-Catenin/Axin2 pathway. Cancer Res. 76:3364–3375. 2016. View Article : Google Scholar : PubMed/NCBI
15	Shi M, Cao M, Song J, Liu Q, Li H, Meng F, Pan Z, Bai J and Zheng J: PinX1 inhibits the invasion and metastasis of human breast cancer via suppressing NF-κB/MMP-9 signaling pathway. Mol Cancer. 14:662015. View Article : Google Scholar : PubMed/NCBI
16	D'Angelo RC, Ouzounova M, Davis A, Choi D, Tchuenkam SM, Kim G, Luther T, Quraishi AA, Senbabaoglu Y, Conley SJ, et al: Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity. Mol Cancer Ther. 14:779–787. 2015. View Article : Google Scholar : PubMed/NCBI
17	Zhang W and Grivennikov SI: Top Notch cancer stem cells by paracrine NF-κB signaling in breast cancer. Breast Cancer Res. 15:3162013. View Article : Google Scholar : PubMed/NCBI
18	Zhang Q, Yuan Y, Cui J, Xiao T and Jiang D: Paeoniflorin inhibits proliferation and invasion of breast cancer cells through suppressing Notch-1 signaling pathway. Biomed Pharmacother. 78:197–203. 2016. View Article : Google Scholar : PubMed/NCBI
19	Pei J and Wang B: Notch-1 promotes breast cancer cells proliferation by regulating LncRNA GAS5. Int J Clin Exp Med. 8:14464–14471. 2015.PubMed/NCBI
20	Xu J, Song F, Jin T, Qin J, Wu J, Wang M, Wang Y and Liu J: Prognostic values of Notch receptors in breast cancer. Tumour Biol. 37:1871–1877. 2016. View Article : Google Scholar : PubMed/NCBI
21	Vinson KE, George DC, Fender AW, Bertrand FE and Sigounas G: The Notch pathway in colorectal cancer. Int J Cancer. 138:1835–1842. 2016. View Article : Google Scholar : PubMed/NCBI
22	Pant S, Jones SF, Kurkjian CD, Infante JR, Moore KN, Burris HA, McMeekin DS, Benhadji KA, Patel BK, Frenzel MJ, et al: A first-in-human phase I study of the oral Notch inhibitor, LY900009, in patients with advanced cancer. Eur J Cancer. 56:1–9. 2016. View Article : Google Scholar : PubMed/NCBI
23	Mizuma M, Rasheed ZA, Yabuuchi S, Omura N, Campbell NR, de Wilde RF, De Oliveira E, Zhang Q, Puig O, Matsui W, et al: The gamma secretase inhibitor MRK-003 attenuates pancreatic cancer growth in preclinical models. Mol Cancer Ther. 11:1999–2009. 2012. View Article : Google Scholar : PubMed/NCBI
24	Jiang X, Li T and Liu RH: 2α-Hydroxyursolic acid inhibited cell proliferation and induced apoptosis in MDA-MB-231 human breast cancer cells through the p38/MAPK signal transduction pathway. J Agric Food Chem. 64:1806–1816. 2016. View Article : Google Scholar : PubMed/NCBI
25	Wang HT and Wang CQ: 27-O-(E)-p-coumaric acyl ursolic acid via JNK/SAPK signal pathway regulates apoptosis of human breast cancer MDA-MB-231 cell line. Zhongguo Zhong Yao Za Zhi. 40:722–726. 2015.(In Chinese). PubMed/NCBI
26	Zhang Y, Song M, Cui ZS, Li CY, Xue XX, Yu M, Lu Y, Zhang SY, Wang EH and Wen YY: Down-regulation of TSG101 by small interfering RNA inhibits the proliferation of breast cancer cells through the MAPK/ERK signal pathway. Histol Histopathol. 26:87–94. 2011.PubMed/NCBI
27	Lin YJ, Huang YH, Zhen YZ, Liu XJ and Zhen YS: Rhein lysinate induces apoptosis in breast cancer SK-Br-3 cells by inhibiting HER-2 signal pathway. Yao Xue Xue Bao. 43:1099–1105. 2008.(In Chinese). PubMed/NCBI
28	Zhou X, Teng L and Wang M: Distinct prognostic values of four-Notch-receptor mRNA expression in ovarian cancer. Tumour Biol. 37:6979–6985. 2016. View Article : Google Scholar : PubMed/NCBI
29	Ranogajec I, Jakić-Razumović J, Puzović V and Gabrilovac J: Prognostic value of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and aminopeptidase N/CD13 in breast cancer patients. Med Oncol. 29:561–569. 2012. View Article : Google Scholar : PubMed/NCBI
30	Yi SJ, Li LL and Tu WB: MiR-214 negatively regulates proliferation and WNT/β-catenin signaling in breast cancer. Eur Rev Med Pharmacol Sci. 20:5148–5154. 2016.PubMed/NCBI
31	Huang Y, Zhao K, Hu Y, Zhou Y, Luo X, Li X, Wei L, Li Z, You Q, Guo Q and Lu N: Wogonoside inhibits angiogenesis in breast cancer via suppressing Wnt/β-catenin pathway. Mol Carcinog. 55:1598–1612. 2016. View Article : Google Scholar : PubMed/NCBI