TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer

  • Authors:
    • Zhuo Deng
    • Jiancheng Zhou
    • Xi Han
    • Xu Li
  • View Affiliations

  • Published online on: November 3, 2015     https://doi.org/10.3892/or.2015.4388
  • Pages: 359-365
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Abstract

Targeted therapy has revolutionized the therapeutic landscape in oncology in recent years and anti-VEGF agent has been approved for ovarian cancer (OC). Unfortunately, the efficacy of this treatment is limited due to the development of resistance, while the molecular mechanisms underlying OC resistance to anti-VEGF therapy are less clear. In this study, we observed a differential response of OC cells to anti-VEGF agent bevacizumab (BV) by using xenograft models. Gene expression analysis showed that TCEB2 gene was significantly upregulated in the OC tumors with acquired resistance compared with the sensitive tumors. Further mechanism dissections demonstrated that TCEB2 played a critical role in the development of acquired resistance to BV in OC cells via promoting HIF-1α degradation and suppressing VEGF-A expression. In TCEB2 overexpressing cells, interleukin-8 (IL-8) was elevated and functioned as a compensatory angiogenesis signaling which was sensitive to IL-8 monoclonal antibody (IL-8 Ab). The combination of BV and IL-8 Ab exhibited synergistic effect of growth inhibition on both OC and endothelial cells. Thus, this study provides an alternative strategy of simultaneously targeting VEGF-A and IL-8 for combating OC.
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January-2016
Volume 35 Issue 1

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

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Spandidos Publications style
Deng Z, Zhou J, Han X and Li X: TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer. Oncol Rep 35: 359-365, 2016
APA
Deng, Z., Zhou, J., Han, X., & Li, X. (2016). TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer. Oncology Reports, 35, 359-365. https://doi.org/10.3892/or.2015.4388
MLA
Deng, Z., Zhou, J., Han, X., Li, X."TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer". Oncology Reports 35.1 (2016): 359-365.
Chicago
Deng, Z., Zhou, J., Han, X., Li, X."TCEB2 confers resistance to VEGF‑targeted therapy in ovarian cancer". Oncology Reports 35, no. 1 (2016): 359-365. https://doi.org/10.3892/or.2015.4388