HIF-1α/MDR1 pathway confers chemoresistance to cisplatin in bladder cancer

  • Authors:
    • Yi Sun
    • Zhenfeng Guan
    • Liang Liang
    • Yongyi Cheng
    • Jiancheng Zhou
    • Jing Li
    • Yonggang Xu
  • View Affiliations

  • Published online on: December 29, 2015     https://doi.org/10.3892/or.2015.4536
  • Pages: 1549-1556
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Bladder cancer (BCa) is the 9th most common malignant tumor and the 13th leading cause of death due to cancer. The development of surgery and target drugs bring new challenges for the traditional concept for BCa therapy, and chemotherapy is still the final option for many BCa patients, and cisplatin-containing regimen the most effective one. However, the ubiquitous application of cisplatin-containing regimen in BCa results in the cisplatin-resistance, in addition, the cisplatin‑resistant BCa manifests enhanced malignant behavior, the mechanism of which is unclear. In the present study, we used BCa cell lines to to clarify this point. BCa cell lines T24/J82 were pretreated with cisplatin >3 months to construct stable cisplatin-resistant cell lines (tagged T24Cis-R and J82Cis-R), which manifested as enhanced capacity of proliferation and malignant behavior in vivo and in vitro, accompanied by cisplatin, and even doxorubicin resistance. The following mechanism dissection revealed that prolonged treatment time of T24/J82 cells led to elevated expression of HIF-1α, which targeted the increased expression of MDR1 on the one hand, and contributed to BCa cell proliferation, migration/invasion on the other hand. Finally, IHC staining of human BCa tissue supported our conclusion that the expression of HIF-1α and MDR1 was higher in chemoresistant tissue vs. chemosensitive tissue. Our results provided a new view of HIF-1α in chemotherapy.
View Figures
View References

Related Articles

Journal Cover

March-2016
Volume 35 Issue 3

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Sun Y, Guan Z, Liang L, Cheng Y, Zhou J, Li J and Xu Y: HIF-1α/MDR1 pathway confers chemoresistance to cisplatin in bladder cancer. Oncol Rep 35: 1549-1556, 2016
APA
Sun, Y., Guan, Z., Liang, L., Cheng, Y., Zhou, J., Li, J., & Xu, Y. (2016). HIF-1α/MDR1 pathway confers chemoresistance to cisplatin in bladder cancer. Oncology Reports, 35, 1549-1556. https://doi.org/10.3892/or.2015.4536
MLA
Sun, Y., Guan, Z., Liang, L., Cheng, Y., Zhou, J., Li, J., Xu, Y."HIF-1α/MDR1 pathway confers chemoresistance to cisplatin in bladder cancer". Oncology Reports 35.3 (2016): 1549-1556.
Chicago
Sun, Y., Guan, Z., Liang, L., Cheng, Y., Zhou, J., Li, J., Xu, Y."HIF-1α/MDR1 pathway confers chemoresistance to cisplatin in bladder cancer". Oncology Reports 35, no. 3 (2016): 1549-1556. https://doi.org/10.3892/or.2015.4536