Ursolic acid inhibits proliferation and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hypoxia-inducible factor-1α in vitro

  • Authors:
    • Wen-Jing Wang
    • Hua Sui
    • Cong Qi
    • Qi Li
    • Jie Zhang
    • Shao-Fei Wu
    • Ming-Zhu Mei
    • Ying-Yu Lu
    • Yi-Ting Wan
    • Hannah Chang
    • Piao-Ting Guo
  • View Affiliations

  • Published online on: May 18, 2016     https://doi.org/10.3892/or.2016.4813
  • Pages: 428-440
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Hypoxia in tumors is closely related to drug resistance. It has not been verified whether hypoxia-inducible factor-1α (HIF-1α) or ABCG2 is related to hypoxia-induced resistance. Ursolic acid (UA), when used in combination with cisplatin can significantly increase the sensitivity of ovarian cancer stem cells (CSCs) to cisplatin, but the exact mechanism is unknown. The cell growth inhibitory rate of cisplatin under different conditions was evaluated using Cell Counting Kit-8 (CCK-8) in adherence and sphere cells (SKOV3, A2780, and HEY). The expression of HIF-1α and ABCG2 was tested using quantitative PCR, western blotting, and immuno­fluorescence under different culture conditions and treated with UA. Knockdown of HIF-1α by shRNA and LY294002 was used to inhibit the activity of PI3K/Akt pathway. Ovarian CSCs express stemness-related genes and drug resistance significantly higher than normal adherent cells. Under hypoxic conditions, the ovarian CSCs grew faster and were more drug resistant than under normoxia. UA could inhibit proliferation and reverse the drug resistance of ovarian CSC by suppressing ABCG2 and HIF-1α under different culture conditions. HIF-1α inhibitor YC-1 combined with UA suppressed the stemness genes and ABCG2 under hypoxic condition. The PI3K/Akt signaling pathway activation plays an important functional role in UA-induced downregulation of HIF-1α and reduction of ABCG2. UA inhibits the proliferation and reversal of drug resistance in ovarian CSCs by suppressing the expression of downregulation of HIF-1α and ABCG2.
View Figures
View References

Related Articles

Journal Cover

July-2016
Volume 36 Issue 1

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
Wang W, Sui H, Qi C, Li Q, Zhang J, Wu S, Mei M, Lu Y, Wan Y, Chang H, Chang H, et al: Ursolic acid inhibits proliferation and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hypoxia-inducible factor-1α in vitro. Oncol Rep 36: 428-440, 2016
APA
Wang, W., Sui, H., Qi, C., Li, Q., Zhang, J., Wu, S. ... Guo, P. (2016). Ursolic acid inhibits proliferation and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hypoxia-inducible factor-1α in vitro. Oncology Reports, 36, 428-440. https://doi.org/10.3892/or.2016.4813
MLA
Wang, W., Sui, H., Qi, C., Li, Q., Zhang, J., Wu, S., Mei, M., Lu, Y., Wan, Y., Chang, H., Guo, P."Ursolic acid inhibits proliferation and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hypoxia-inducible factor-1α in vitro". Oncology Reports 36.1 (2016): 428-440.
Chicago
Wang, W., Sui, H., Qi, C., Li, Q., Zhang, J., Wu, S., Mei, M., Lu, Y., Wan, Y., Chang, H., Guo, P."Ursolic acid inhibits proliferation and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hypoxia-inducible factor-1α in vitro". Oncology Reports 36, no. 1 (2016): 428-440. https://doi.org/10.3892/or.2016.4813