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Article Open Access

Doxorubicin combined with Notch1‑targeting siRNA for the treatment of gastric cancer

  • Authors:
    • Wei Zhou
    • Wei Tan
    • Xu Huang
    • Hong Gang Yu
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
    Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2805-2812
    |
    Published online on: June 28, 2018
       https://doi.org/10.3892/ol.2018.9039
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Abstract

Notch1, a transmembrane receptor that has a notable role in gastric cancer (GC) as an oncogene, has been reported to be involved in doxorubicin resistance. Thus, Notch1 is a potential therapeutic target for GC. In the present study, the protein levels of Notch1 intracellular domain (NICD; a marker of Notch1 activation) in human GC cell lines and tumor tissues was measured by western blotting. Next, the effects of Notch1 depletion in SGC7901 cells were evaluated. Finally, the efficacy of Notch1 small interfering RNA (siRNA) combined with doxorubicin therapy for GC was examined in vitro and in vivo. The results revealed that NICD levels were high in GC cells, and that the inhibition of NICD by transfection with Notch1 siRNA induced apoptosis and inhibited proliferation. Ectopic downregulation of Notch1 expression enhanced the sensitivity of GC tumors to doxorubicin, which suppressed the development of GC. These data demonstrated that Notch1 was a significant regulator of cell proliferation and apoptosis in GC. Thus, the combination of doxorubicin with Notch1 siRNA is a potential strategy for the treatment of GC.
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1 

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Kang Y, Li S, Ge Q, Liu X, Yang Z, Xue Y and Wang F: Extent of serosal changes predicts peritoneal recurrence and poor prognosis after curative surgery for gastric cancer. Medicine (Baltimore). 94:e17502015. View Article : Google Scholar : PubMed/NCBI

3 

Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A and Fleig WE: Chemotherapy in advanced gastric cancer: A systematic review and meta-analysis based on aggregate data. J Clin Oncol. 24:2903–2909. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Tacar O, Sriamornsak P and Dass CR: Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol. 65:157–170. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Xu J, Liu D, Niu H, Zhu G, Xu Y, Ye D, Li J and Zhang Q: Resveratrol reverses Doxorubicin resistance by inhibiting epithelial-mesenchymal transition (EMT) through modulating PTEN/Akt signaling pathway in gastric cancer. J Exp Clin Cancer Res. 36:192017. View Article : Google Scholar : PubMed/NCBI

6 

Zhou Q, Wang Y, Peng B, Liang L and Li J: The roles of Notch1 expression in the migration of intrahepatic cholangiocarcinoma. BMC Cancer. 13:2442013. View Article : Google Scholar : PubMed/NCBI

7 

Ke Z, Mao X, Li S, Wang R, Wang L and Zhao G: Dynamic expression characteristics of Notch signal in bone marrow-derived mesenchymal stem cells during the process of differentiation into hepatocytes. Tissue Cell. 45:95–100. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Qiu H, Tang X, Ma J, Shaverdashvili K, Zhang K and Bedogni B: Notch1 autoactivation via transcriptional regulation of furin, which sustains Notch1 signaling by processing Notch1-activating proteases ADAM10 and membrane type 1 matrix metalloproteinase. Mol Cell Biol. 35:3622–32. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Soylu H, Acar N, Ozbey O, Unal B, Koksal IT, Bassorgun I, Ciftcioglu A and Ustunel I: Characterization of Notch signalling pathway members in normal prostate, prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma. Pathol Oncol Res. 22:87–94. 2016. View Article : Google Scholar : PubMed/NCBI

10 

Colomer-Lahiguera S and Strehl S: Complexity of NOTCH1 juxtamembrane insertion mutations in T-cell acute lymphoblastic leukemia. Leuk Lymphoma. 57:1219–1222. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Rodriguez JM, Miranda D, Bunout D, Ronco AM, de la Maza MP and Hirsch S: Folates induce colorectal carcinoma HT29 cell line proliferation through Notch1 signaling. Nutr Cancer. 67:706–711. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Hassan WA, Yoshida R, Kudoh S, Hasegawa K, Niimori-Kita K and Ito T: Notch1 controls cell invasion and metastasis in small cell lung carcinoma cell lines. Lung Cancer. 86:304–310. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Yeh TS, Wu CW, Hsu KW, Liao WJ, Yang MC, Li AF, Wang AM, Kuo ML and Chi CW: The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2. Cancer Res. 69:5039–5048. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Harada K, Sato Y, Ikeda H, Hsu M, Igarashi S and Nakanuma Y: Notch1-Hes1 signalling axis in the tumourigenesis of biliary neuroendocrine tumours. J Clin Pathol. 66:386–391. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Pedrosa AR, Graça JL, Carvalho S, Peleteiro MC, Duarte A and Trindade A: Notch signaling dynamics in the adult healthy prostate and in prostatic tumor development. Prostate. 76:80–96. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Hassan WA, Yoshida R, Kudoh S, Kameyama H, Hasegawa K, Niimori-Kita K and Ito T: Notch1 controls cell chemoresistance in small cell lung carcinoma cells. Thorac Cancer. 7:123–128. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Lian W, Zhang L, Yang L and Chen W: AP-2α reverses vincristine-induced multidrug resistance of SGC7901 gastric cancer cells by inhibiting the Notch pathway. Apoptosis. 22:933–941. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Zhou W, Fu XQ, Zhang LL, Zhang J, Huang X, Lu XH, Shen L, Liu BN, Liu J, Luo HS, et al: The AKT1/NF-kappaB/Notch1/PTEN axis has an important role in chemoresistance of gastric cancer cells. Cell Death Dis. 4:e8472013. View Article : Google Scholar : PubMed/NCBI

19 

Zhang XS, Hu YH, Gao HY, Lan XW and Xue YW: Downregulation of Notch1 inhibits the invasion and metastasis of human gastric cancer cells SGC7901 and MKN74 in vitro through PTEN activation and dephosphorylation of Akt and FAK. Mol Med Rep. 16:2318–2324. 2017. View Article : Google Scholar : PubMed/NCBI

20 

World Medical Association, . World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 310:2191–2194. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Wang M, Chen DQ, Chen L, Liu D, Zhao H, Zhang ZH, Vaziri ND, Guo Y, Zhao YY and Cao G: Novel RAS inhibitors poricoic acid ZG and poricoic acid ZH attenuate renal fibrosis via Wnt/β-catenin pathway and targeted phosphorylation smad3 signaling. J Agric Food Chem. 66:1828–1842. 2018. View Article : Google Scholar : PubMed/NCBI

22 

National Research Council, . Committee for the Update of the Guide for the Care and Use of Laboratory, Institute for Laboratory Animal Research and Division on Earth and Life Studies: Guide for the Care and Use of Laboratory Animals. 8th edition. The National Academies Press; Washington, DC: 2011

23 

Fender AW, Nutter JM, Fitzgerald TL, Bertrand FE and Sigounas G: Notch-1 promotes stemness and epithelial to mesenchymal transition in colorectal cancer. J Cell Biochem. 116:2517–2527. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Hsu KW, Hsieh RH, Huang KH, Li Fen-Yau A, Chi CW, Wang TY, Tseng MJ, Wu KJ and Yeh TS: Activation of the Notch1/STAT3/Twist signaling axis promotes gastric cancer progression. Carcinogenesis. 33:1459–1467. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Zhang H, Wang X, Xu J and Sun Y: Notch1 activation is a poor prognostic factor in patients with gastric cancer. Br J Cancer. 110:2283–2290. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Villasmil ML, Francisco J, Gallo-Ebert C, Donigan M, Liu HY, Brower M and Nickels JT Jr: Ceramide signals for initiation of yeast mating-specific cell cycle arrest. Cell Cycle. 15:441–454. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Seo JH, Jeong ES and Choi YK: Therapeutic effects of lentivirus-mediated shRNA targeting of cyclin D1 in human gastric cancer. BMC Cancer. 14:1752014. View Article : Google Scholar : PubMed/NCBI

28 

Vadde R, Radhakrishnan S, Reddivari L and Vanamala JK: Triphala extract suppresses proliferation and induces apoptosis in human colon cancer stem cells via Suppressing c-Myc/Cyclin D1 and elevation of Bax/Bcl-2 ratio. Biomed Res Int. 2015:6492632015. View Article : Google Scholar : PubMed/NCBI

29 

Liu E, Liang T, Wang X, Ban S, Han L and Li Q: Apoptosis induced by farrerol in human gastric cancer SGC-7901 cells through the mitochondrial-mediated pathway. Eur J Cancer Prev. 24:365–372. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Choi JH, Lim HY, Joo HJ, Kim HS, Yi JW, Kim HC, Cho YK, Kim MW and Lee KB: Expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection. Br J Cancer. 86:1578–1585. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Yu HG, Ai YW, Yu LL, Zhou XD, Liu J, Li JH, Xu XM, Liu S, Chen J, Liu F, et al: Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death. Int J Cancer. 122:433–443. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Cui J, Jiang W, Wang S, Wang L and Xie K: Role of Wnt/β-catenin signaling in drug resistance of pancreatic cancer. Curr Pharm Des. 18:2464–2471. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Tang KD and Ling MT: Targeting drug-resistant prostate cancer with dual PI3K/mTOR inhibition. Curr Med Chem. 21:3048–3056. 2013. View Article : Google Scholar

34 

Zhao Y and Yang X: The Hippo pathway in chemotherapeutic drug resistance. Int J Cancer. 137:2767–2773. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Broxterman HJ, Gotink KJ and Verheul HM: Understanding the causes of multidrug resistance in cancer: A comparison of doxorubicin and sunitinib. Drug Resist Updat. 12:114–126. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Kang X, Li M, Zhu H, Lu X, Miao J, Du S, Xia X and Guan W: DUSP4 promotes doxorubicin resistance in gastric cancer through epithelial-mesenchymal transition. Oncotarget. 8:94028–94039. 2017.PubMed/NCBI

37 

Wagner W, Kania KD, Blauz A and Ciszewski WM: The lactate receptor (HCAR1/GPR81) contributes to doxorubicin chemoresistance via ABCB1 transporter up-regulation in human cervical cancer HeLa cells. J Physiol Pharmacol. 68:555–564. 2017.PubMed/NCBI

38 

Rizzo S, Cangemi A, Galvano A, Fanale D, Buscemi S, Ciaccio M, Russo A, Castorina S and Bazan V: Analysis of miRNA expression profile induced by short term starvation in breast cancer cells treated with doxorubicin. Oncotarget. 8:71924–71932. 2017. View Article : Google Scholar : PubMed/NCBI

39 

Kotiyal S and Bhattacharya S: Breast cancer stem cells, EMT and therapeutic targets. Biochem Biophys Res Commun. 453:112–116. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhou W, Tan W, Huang X and Yu HG: Doxorubicin combined with Notch1‑targeting siRNA for the treatment of gastric cancer. Oncol Lett 16: 2805-2812, 2018.
APA
Zhou, W., Tan, W., Huang, X., & Yu, H.G. (2018). Doxorubicin combined with Notch1‑targeting siRNA for the treatment of gastric cancer. Oncology Letters, 16, 2805-2812. https://doi.org/10.3892/ol.2018.9039
MLA
Zhou, W., Tan, W., Huang, X., Yu, H. G."Doxorubicin combined with Notch1‑targeting siRNA for the treatment of gastric cancer". Oncology Letters 16.3 (2018): 2805-2812.
Chicago
Zhou, W., Tan, W., Huang, X., Yu, H. G."Doxorubicin combined with Notch1‑targeting siRNA for the treatment of gastric cancer". Oncology Letters 16, no. 3 (2018): 2805-2812. https://doi.org/10.3892/ol.2018.9039
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou W, Tan W, Huang X and Yu HG: Doxorubicin combined with Notch1‑targeting siRNA for the treatment of gastric cancer. Oncol Lett 16: 2805-2812, 2018.
APA
Zhou, W., Tan, W., Huang, X., & Yu, H.G. (2018). Doxorubicin combined with Notch1‑targeting siRNA for the treatment of gastric cancer. Oncology Letters, 16, 2805-2812. https://doi.org/10.3892/ol.2018.9039
MLA
Zhou, W., Tan, W., Huang, X., Yu, H. G."Doxorubicin combined with Notch1‑targeting siRNA for the treatment of gastric cancer". Oncology Letters 16.3 (2018): 2805-2812.
Chicago
Zhou, W., Tan, W., Huang, X., Yu, H. G."Doxorubicin combined with Notch1‑targeting siRNA for the treatment of gastric cancer". Oncology Letters 16, no. 3 (2018): 2805-2812. https://doi.org/10.3892/ol.2018.9039
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