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Combined aspirin and apatinib treatment suppresses gastric cancer cell proliferation

  • Authors:
    • Wei Zhang
    • Yongsheng Tan
    • Heping Ma

  • View Affiliations

  • Published online on: August 31, 2017     https://doi.org/10.3892/ol.2017.6858
  • Pages: 5409-5417

  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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November-2017
Volume 14 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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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