Effect of arenobufagin on human pancreatic carcinoma cells

  • Authors:
    • Tianjiao Wang
    • Zhumei Zhuang
    • Peng Zhang
    • Yueyue Wang
    • Lin Mu
    • Haifeng Jin
    • Lei Zhou
    • Xiaochi Ma
    • Rui Liang
    • Yuhui Yuan
  • View Affiliations

  • Published online on: August 23, 2017     https://doi.org/10.3892/ol.2017.6798
  • Pages: 4971-4976
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Abstract

Pancreatic carcinoma (PC) is a deadly form of cancer with poor overall survival. Currently, chemotherapy such as gemcitabine and 5‑fluorouracil (5‑FU) are the most popular medications that can improve survival, but rapid drug‑resistance makes the search for more effective drugs urgent. Upon looking for natural components to treat PC, it was found that arenobufagin, a cardiac glycosides‑like compound, showed significant effects on the gemcitabine‑resistant pancreatic carcinoma cell line Panc‑1 and the gemcitabine‑sensitive cell line ASPC‑1 at nanomolar concentrations. The present study used MTT and clonogenic survival assays to examine survival and proliferation, and western blotting to assess changes in the associated mitogen activated protein kinase and phosphoinositide 3‑kinase pathways and expression of apoptosis‑related proteins. The current study also detected the cell cycle by flow cytometry. Arenobufagin inhibited cell survival and proliferation, decreased the phosphorylation of key downstream proteins of K‑Ras, including protein kinase B and extracellular signal related kinase, induced cell cycle G2/M phase arrest and apoptosis, and downregulated the level of phosphorylated epidermal growth factor receptor. Notably, the present data also showed that arenobufagin can enhance the sensitivity of PC cells to gemcitabine and 5‑FU. In conclusion, arenobufagin could enhance the effect of gemcitabine and 5‑FU on PC cells by targeting multiple key proteins. Therefore, arenobufagin has potential as anadjuvant therapy for the treatment of PC.
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October-2017
Volume 14 Issue 4

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

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Spandidos Publications style
Wang T, Zhuang Z, Zhang P, Wang Y, Mu L, Jin H, Zhou L, Ma X, Liang R, Yuan Y, Yuan Y, et al: Effect of arenobufagin on human pancreatic carcinoma cells. Oncol Lett 14: 4971-4976, 2017
APA
Wang, T., Zhuang, Z., Zhang, P., Wang, Y., Mu, L., Jin, H. ... Yuan, Y. (2017). Effect of arenobufagin on human pancreatic carcinoma cells. Oncology Letters, 14, 4971-4976. https://doi.org/10.3892/ol.2017.6798
MLA
Wang, T., Zhuang, Z., Zhang, P., Wang, Y., Mu, L., Jin, H., Zhou, L., Ma, X., Liang, R., Yuan, Y."Effect of arenobufagin on human pancreatic carcinoma cells". Oncology Letters 14.4 (2017): 4971-4976.
Chicago
Wang, T., Zhuang, Z., Zhang, P., Wang, Y., Mu, L., Jin, H., Zhou, L., Ma, X., Liang, R., Yuan, Y."Effect of arenobufagin on human pancreatic carcinoma cells". Oncology Letters 14, no. 4 (2017): 4971-4976. https://doi.org/10.3892/ol.2017.6798