Maslinic acid potentiates the antitumor activities of gemcitabine in vitro and in vivo by inhibiting NF-κB-mediated survival signaling pathways in human gallbladder cancer cells

  • Authors:
    • Yong Yu
    • Jinghan Wang
    • Nianxin Xia
    • Bin Li
    • Xiaoqing Jiang
  • View Affiliations

  • Published online on: January 28, 2015     https://doi.org/10.3892/or.2015.3755
  • Pages: 1683-1690
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Gemcitabine (GEM) is one of the first-line drugs in the treatment of gallbladder cancer (GBC), although the therapeutic effect is not sustained due to resistance to the drug over time. Maslinic acid (MA) has been shown to inhibit transcription factor nuclear factor-κB (NF-κB), resulting in the suppression of survival signaling. The authors of the present study investigated whether MA enhanced the antitumor activity of GEM in GBC. Anti-proliferative effects of MA, GEM and MA + GEM were assessed using the MTT assay. Apoptosis was assessed using Annexin V and by western blot analysis of various mediators of apoptosis. Xenograft tumors of EH-GB2 GBC cells were established in athymic nude mice and were monitored following treatment with MA, GEM and MA + GEM. Immunohistochemistry of the tumors was used to examine various survival proteins. MA inhibited the in vitro proliferation of various GBC cell lines and potentiated the apoptosis and cell invasion inhibition induced by GEM. Western blot analysis showed that the combination of MA and GEM inhibited constitutive NF-κB activation and NF-κB-regulated gene products, including cyclin D1, Bcl-2, Bax, MMP-2 and MMP-9, to a greater extent. In vivo, the group that was treated with MA + GEM showed significant reductions in tumor volume and a decreased expression of NF-κB-regulated gene products. In conclusion, the results suggest that MA potentiates the antitumor effects of GEM in human GBC cell lines by suppressing the activation of NF-κB and its dowstream gene products, which are involved in survival signaling.
View Figures
View References

Related Articles

Journal Cover

April-2015
Volume 33 Issue 4

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
Yu Y, Wang J, Xia N, Li B and Jiang X: Maslinic acid potentiates the antitumor activities of gemcitabine in vitro and in vivo by inhibiting NF-κB-mediated survival signaling pathways in human gallbladder cancer cells. Oncol Rep 33: 1683-1690, 2015
APA
Yu, Y., Wang, J., Xia, N., Li, B., & Jiang, X. (2015). Maslinic acid potentiates the antitumor activities of gemcitabine in vitro and in vivo by inhibiting NF-κB-mediated survival signaling pathways in human gallbladder cancer cells. Oncology Reports, 33, 1683-1690. https://doi.org/10.3892/or.2015.3755
MLA
Yu, Y., Wang, J., Xia, N., Li, B., Jiang, X."Maslinic acid potentiates the antitumor activities of gemcitabine in vitro and in vivo by inhibiting NF-κB-mediated survival signaling pathways in human gallbladder cancer cells". Oncology Reports 33.4 (2015): 1683-1690.
Chicago
Yu, Y., Wang, J., Xia, N., Li, B., Jiang, X."Maslinic acid potentiates the antitumor activities of gemcitabine in vitro and in vivo by inhibiting NF-κB-mediated survival signaling pathways in human gallbladder cancer cells". Oncology Reports 33, no. 4 (2015): 1683-1690. https://doi.org/10.3892/or.2015.3755