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Combined aspirin and apatinib treatment suppresses gastric cancer cell proliferation

  • Authors:
    • Wei Zhang
    • Yongsheng Tan
    • Heping Ma
  • View Affiliations / Copyright

    Affiliations: Department of Intervention Division, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia 010017, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5409-5417
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    Published online on: August 31, 2017
       https://doi.org/10.3892/ol.2017.6858
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Abstract

Gastric cancer (GC), one of the types of tumor most prone to malignancy, is characterized by high lethality. Numerous molecular mediators of GC have been identified, including transcription factors, signaling molecules and non‑coding RNAs. Recently, inhibition of angiogenesis has emerged as a potential strategy for GC therapy. In the present study, the levels of vascular endothelial growth factor (VEGF), peroxisome proliferator‑activated receptor‑α (PPARα) and miR‑21 in GC patients and individuals without cancer, and the correlation between VEGF and miR‑21, and PPARα and miR‑21 expression were analyzed. In addition, the GC MKN45 cell line was treated with apatinib (a tyrosine kinase inhibitor) and aspirin (an activator of the transcription factor, PPARα) to investigate the effects of these compounds on tumorigenesis. Furthermore, the present study attempted to elucidate the molecular mechanisms of alteration of GC tumorigenesis by aspirin and apatinib. The results of the current study demonstrated that there was a higher expression of VEGF and miR‑21 in GC tissues compared with that in morphologically adjacent normal tissues whereas PPARα expression was decreased. These results were confirmed in vitro, as treatment of MKN45 cells with VEGF resulted in a significant increase in miR‑21 expression and a significant reduction in PPARα protein expression. Furthermore, the inhibitory effects of VEGF on PPARα mRNA and protein expression were demonstrated to be mediated by miR‑21. Suppression of PPARα protein expression attenuated the inhibitory effects of miR‑21 on the level of PPARα mRNA, thereby enhancing tumorigenesis in gastric cancer. Treatment of MKN45 cells with aspirin reduced the levels of phosphorylated AKT by activating PPARα, whereas treatment with apatinib inhibited the phosphorylation of vascular endothelial growth factor receptor 2 and phosphoinositide‑3 kinase in MKN45 cells. Finally, treatment of MKN45 cells with apatinib and aspirin suppressed tumorigenesis by inhibiting cell proliferation, migration, invasion and colony formation. Taken together, the results of the present study indicate that treatment with a combination of aspirin and apatinib may be a potential therapeutic strategy for GC treatment.
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1 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J and Fleig WE: Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 17:CD0040642010.

3 

Petrioli R, Francini E, Roviello F, Marrelli D, Fiaschi AI, Laera L, Rossi G, Bianco V, Brozzetti S and Roviello G: Sequential treatment with epirubicin, oxaliplatin and 5FU (EOF) followed by docetaxel, oxaliplatin and 5FU (DOF) in patients with advanced gastric or gastroesophageal cancer: A single-institution experience. Cancer Chemother Pharmacol. 75:941–947. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Ebos JM, Bocci G, Man S, Thorpe PE, Hicklin DJ, Zhou D, Jia X and Kerbel RS: A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma. Mol Cancer Res. 2:315–326. 2004.PubMed/NCBI

5 

Hicklin DJ and Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 23:1011–1027. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Holmes K, Roberts OL, Thomas AM and Cross MJ: Vascular endothelial growth factor receptor-2: Structure, function, intracellular signaling and therapeutic inhibition. Cell Signal. 19:2003–2012. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, et al: Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 34:1448–1454. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Ilson DH: Targeting the vascular endothelial growth factor pathway in gastric cancer: A hit or a miss? J Clin Oncol. 34:1431–1432. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Chang H, Kim N, Park JH, Nam RH, Choi YJ, Lee HS, Yoon H, Shin CM, Park YS, Kim JM and Lee DH: Different microRNA expression levels in gastric cancer depending on Helicobacter pylori infection. Gut Liver. 9:188–196. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Lin S and Gregory RI: MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 15:321–333. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Suárez Y and Sessa WC: MicroRNAs as novel regulators of angiogenesis. Circ Res. 104:442–454. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Liu LZ, Li C, Chen Q, Jing Y, Carpenter R, Jiang Y, Kung HF, Lai L and Jiang BH: miR-21 induced angiogenesis through AKT and ERK activation and HIF-1α expression. PLoS One. 6:e191392011. View Article : Google Scholar : PubMed/NCBI

13 

Jiang FS, Tian SS, Lu JJ, Ding XH, Qian CD, Ding B, Ding ZS and Jin B: Cardamonin Regulates miR-21 expression and suppresses angiogenesis induced by vascular endothelial growth factor. Biomed Res Int. 2015:5015812015. View Article : Google Scholar : PubMed/NCBI

14 

Zhou J, Wang KC, Wu W, Subramaniam S, Shyy JY, Chiu JJ, Li JY and Chien S: MicroRNA-21 targets peroxisome proliferators-activated receptor alpha in an autoregulatory loop to modulate flow-induced endothelial inflammation. Proc Natl Acad Sci USA. 108:10355–10360. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Kersten S, Desvergne B and Wahli W: Roles of PPARs in health and disease. Nature. 405:421–424. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Kim JH, Kim T, Qu A and Gonzalez FJ: Abstract 23: Nuclear receptor PPARα activation triggers hepatic cell death in Ikkβ-deficient mice. Cancer Res. 75:232015. View Article : Google Scholar

17 

Aboud Abu O, Donohoe D, Bultman S, Fitch M, Riiff T, Hellerstein M and Weiss RH: PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth. Am J Physiol Cell Physiol. 308:C890–C898. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Chandran K, Goswami S and Sharma-walia N: Implications of a peroxisome proliferator-activated receptor alpha (PPARα) ligand clofibrate in breast cancer. Oncotarget. 7:15577–15599. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Skrypnyk N, Chen X, Hu W, Su Y, Mont S, Yang S, Gangadhariah M, Wei S, Falck JR, Jat JL, et al: PPARα activation can help prevent and treat non-small cell lung cancer. Cancer Res. 74:621–631. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Planagumà A, Titos E, López-Parra M, Gaya J, Pueyo G, Arroyo V and Clària J: Aspirin (ASA) regulates 5-lipoxygenase activity and peroxisome proliferator-activated receptor alpha-mediated CINC-1 release in rat liver cells: Novel actions of lipoxin A4 (LXA4) and ASA-triggered 15-epi-LXA4. FASEB J. 16:1937–1939. 2002.PubMed/NCBI

21 

Søgaard KK, Farkas DK, Pedersen L, Lund JL, Thomsen RW and Sørensen HT: Long-term risk of gastrointestinal cancers in persons with gastric or duodenal ulcers. Cancer Med. 5:1341–1351. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Kim SS, Nam JS, Cho HJ, Won JH, Kim JW, Ji JH, Yang MJ, Park JH, Noh CK, Shin SJ, et al: Plasma microRNA-122 as a predictive marker for treatment response following transarterial chemoembolization in patients with hepatocellular carcinoma. J Gastroenterol Hepatol. 32:199–207. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Zhang W and Li Y: miR-148a downregulates the expression of transforming growth factor-β2 and SMAD2 in gastric cancer. Int J Oncol. 48:1877–1885. 2016.PubMed/NCBI

24 

Fontana E and Smyth EC: Novel targets in the treatment of advanced gastric cancer: A perspective review. Ther Adv Med Oncol. 8:113–125. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Cancer Genome Atlas Research Network: Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 513:202–209. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Roviello G, Petrioli R, Marano L, Polom K, Marrelli D, Perrella A and Roviello F: Angiogenesis inhibitors in gastric and gastroesophageal junction cancer. Gastric Cancer. 19:31–41. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Tian S, Quan H, Xie C, Guo H, Lü F, Xu Y, Li J and Lou L: YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase withpotent activity in vitro and in vivo. Cancer Sci. 102:1374–1380. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Lazăr DC, Tăban S, Cornianu M, Faur A and Goldiş A: New advances in targeted gastric cancer treatment. World J Gastroenterol. 22:6776–6799. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Fornaro L, Vasile E and Falcone A: Apatinib in advanced gastric cancer: A doubtful step forward. J Clin Oncol. Aug 15–2016.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

30 

Luo J, Manning BD and Cantley LC: Targeting the PI3K-Akt pathway in human cancer: Rationale and promise. Cancer Cell. 4:257–262. 2003. View Article : Google Scholar : PubMed/NCBI

31 

Ahmed W, Ziouzenkova O, Brown J, Devchand P, Francis S, Kadakia M, Kanda T, Orasanu G, Sharlach M, Zandbergen F and Plutzky J: PPARs and their metabolic modulation: New mechanisms for transcriptional regulation? J Intern Med. 262:184–198. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Gonzalez FJ and Shah YM: PPARalpha: Mechanism of species differences and hepatocarcinogenesis of peroxisome proliferators. Toxicology. 246:2–8. 2012. View Article : Google Scholar

33 

Hu X, Zhang J, Xu B, Jiang Z, Ragaz J, Tong Z, Zhang Q, Wang X, Feng J, Pang D, et al: Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer. Int J Cancer. 135:1961–1969. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y, Sun G, Yang Y, Wang L, Xu N, et al: Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol. 31:3219–3225. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Sweetman SC: Martindale: The Complete Drug Reference. 37th. Pharmaceutical Press; London, UK: 2011

36 

Algra AM and Rothwell PM: Effects of regular aspirin on long-term cancer incidence and metastasis: A systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol. 13:518–527. 2012. View Article : Google Scholar : PubMed/NCBI

37 

Rothwell PM, Price JF, Fowkes FG, Zanchetti A, Roncaglioni MC, Tognoni G, Lee R, Belch JF, Wilson M, Mehta Z and Meade TW: Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 379:1602–1612. 2012. View Article : Google Scholar : PubMed/NCBI

38 

Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW and Mehta Z: Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomised controlled trials. Lancet. 379:1591–1601. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang W, Tan Y and Ma H: Combined aspirin and apatinib treatment suppresses gastric cancer cell proliferation. Oncol Lett 14: 5409-5417, 2017.
APA
Zhang, W., Tan, Y., & Ma, H. (2017). Combined aspirin and apatinib treatment suppresses gastric cancer cell proliferation. Oncology Letters, 14, 5409-5417. https://doi.org/10.3892/ol.2017.6858
MLA
Zhang, W., Tan, Y., Ma, H."Combined aspirin and apatinib treatment suppresses gastric cancer cell proliferation". Oncology Letters 14.5 (2017): 5409-5417.
Chicago
Zhang, W., Tan, Y., Ma, H."Combined aspirin and apatinib treatment suppresses gastric cancer cell proliferation". Oncology Letters 14, no. 5 (2017): 5409-5417. https://doi.org/10.3892/ol.2017.6858
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang W, Tan Y and Ma H: Combined aspirin and apatinib treatment suppresses gastric cancer cell proliferation. Oncol Lett 14: 5409-5417, 2017.
APA
Zhang, W., Tan, Y., & Ma, H. (2017). Combined aspirin and apatinib treatment suppresses gastric cancer cell proliferation. Oncology Letters, 14, 5409-5417. https://doi.org/10.3892/ol.2017.6858
MLA
Zhang, W., Tan, Y., Ma, H."Combined aspirin and apatinib treatment suppresses gastric cancer cell proliferation". Oncology Letters 14.5 (2017): 5409-5417.
Chicago
Zhang, W., Tan, Y., Ma, H."Combined aspirin and apatinib treatment suppresses gastric cancer cell proliferation". Oncology Letters 14, no. 5 (2017): 5409-5417. https://doi.org/10.3892/ol.2017.6858
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