Tyrphostin B42 attenuates trichostatin A-mediated resistance in pancreatic cancer cells by antagonizing IL-6/JAK2/STAT3 signaling

  • Authors:
    • Xing Zhang
    • Hong Lu
    • Weilong Hong
    • Leping Liu
    • Silu Wang
    • Mengtao Zhou
    • Bicheng Chen
    • Yongheng Bai
  • View Affiliations

  • Published online on: January 31, 2018     https://doi.org/10.3892/or.2018.6241
  • Pages: 1892-1900
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Abstract

Drug-resistance is the key reason for the ineffectiveness of chemotherapy in pancreatic cancer. Thus, it is very important to explore the molecular mechanisms of drug‑resistance and the methods of effective intervention. In the present study, we investigated the effect of tyrphostin B42, also called AG490, on histone deacetylase (HDAC) inhibitor trichostatin A (TSA)‑induced resistance in pancreatic cancer cells (PCCs). Evidence from phase contrast microscope revealed that TSA‑resistant cells (PANC‑1‑TSA) had higher proliferative activity than non‑resistant cells (PANC‑1). This over‑proliferative activity induced by TSA may be associated with abnormal activation of JAK2/STAT3 signaling, which can be strengthened by interleukin‑6 (IL‑6), a STAT3‑upstream inducer, resulting in enhanced expression of STAT3-downstream target genes including c‑Myc, c‑Src, HIF‑1α, and CCND1. In addition, increased expression of Bcl‑2 mRNA and decreased expression of Bax mRNA in PANC‑1‑TSA cells indicated that TSA induced the inhibition of mitochondrial-dependent apoptosis in PCCs. Tyrphostin B42 treatment evidently antagonized the activation of IL‑6/JAK2/STAT3 in a dose‑dependent manner. As a result, tyrphostin B42 inhibited the over‑proliferative activity of PANC‑1‑TSA cells, and downregulated the expression of IL‑6/JAK2/STAT3‑downstream target genes. Moreover, tyrphostin B42 induced the apoptosis of PCCs by regulating the expression of mitochondrial‑related genes. Therefore, these findings demonstrated that tyrphostin B42 attenuated TSA‑mediated resistance in PCCs by antagonizing the IL‑6/JAK2/STAT3 signaling.
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April-2018
Volume 39 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhang X, Lu H, Hong W, Liu L, Wang S, Zhou M, Chen B and Bai Y: Tyrphostin B42 attenuates trichostatin A-mediated resistance in pancreatic cancer cells by antagonizing IL-6/JAK2/STAT3 signaling. Oncol Rep 39: 1892-1900, 2018.
APA
Zhang, X., Lu, H., Hong, W., Liu, L., Wang, S., Zhou, M. ... Bai, Y. (2018). Tyrphostin B42 attenuates trichostatin A-mediated resistance in pancreatic cancer cells by antagonizing IL-6/JAK2/STAT3 signaling. Oncology Reports, 39, 1892-1900. https://doi.org/10.3892/or.2018.6241
MLA
Zhang, X., Lu, H., Hong, W., Liu, L., Wang, S., Zhou, M., Chen, B., Bai, Y."Tyrphostin B42 attenuates trichostatin A-mediated resistance in pancreatic cancer cells by antagonizing IL-6/JAK2/STAT3 signaling". Oncology Reports 39.4 (2018): 1892-1900.
Chicago
Zhang, X., Lu, H., Hong, W., Liu, L., Wang, S., Zhou, M., Chen, B., Bai, Y."Tyrphostin B42 attenuates trichostatin A-mediated resistance in pancreatic cancer cells by antagonizing IL-6/JAK2/STAT3 signaling". Oncology Reports 39, no. 4 (2018): 1892-1900. https://doi.org/10.3892/or.2018.6241