Open Access

α‑hederin overcomes hypoxia‑mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway

  • Authors:
    • Jinbao Chen
    • Jian Xu
    • Jiahua Yang
    • Yueping Zhan
    • Sen Li
    • Linlin Jia
    • Wentao Wu
    • Xianke Si
    • Die Zhang
    • Kun Yu
    • Peihao Yin
    • Yijun Cao
    • Wanli Deng
    • Ke Xu
    • Wei Li
  • View Affiliations

  • Published online on: January 23, 2023     https://doi.org/10.3892/ijo.2023.5481
  • Article Number: 33
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Currently, chemoresistance is a major challenge that directly affects the prognosis of patients with colorectal cancer (CRC). In addition, hypoxia is associated with poor prognosis and therapeutic resistance in patients with cancer. Accumulating evidence has shown that α‑hederin has significant antitumour effects and that α‑hederin can inhibit hypoxia‑mediated drug resistance in CRC; however, the underlying mechanism remains unclear. In the present study, viability and proliferation assays were used to evaluate the effect of α‑hederin on the drug resistance of CRC cells under hypoxia. Sequencing analysis and apoptosis assays were used to determine the effect of α‑hederin on apoptosis under hypoxia. Western blot analysis and reverse transcription‑quantitative PCR were used to measure apoptosis‑related protein and mRNA expression levels. Furthermore, different mouse models were established to study the effect of α‑hederin on hypoxia‑mediated CRC drug resistance in vivo. In the present study, the high expression of Bcl2 in hypoxic CRC cells was revealed to be a key factor in their drug resistance, whereas α‑hederin inhibited the expression of Bcl2 by reducing AKT phosphorylation in vitro and in vivo, and promoted the apoptosis of CRC cells under hypoxia. By contrast, overexpression of AKT reversed the effect of α‑hederin on CRC cell apoptosis under hypoxia. Taken together, these results suggested that α‑hederin may overcome hypoxia‑mediated drug resistance in CRC by inhibiting the AKT/Bcl2 pathway. In the future, α‑hederin may be used as a novel adjuvant for reversing drug resistance in CRC.

Related Articles

Journal Cover

March-2023
Volume 62 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Chen J, Xu J, Yang J, Zhan Y, Li S, Jia L, Wu W, Si X, Zhang D, Yu K, Yu K, et al: α‑hederin overcomes hypoxia‑mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway. Int J Oncol 62: 33, 2023
APA
Chen, J., Xu, J., Yang, J., Zhan, Y., Li, S., Jia, L. ... Li, W. (2023). α‑hederin overcomes hypoxia‑mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway. International Journal of Oncology, 62, 33. https://doi.org/10.3892/ijo.2023.5481
MLA
Chen, J., Xu, J., Yang, J., Zhan, Y., Li, S., Jia, L., Wu, W., Si, X., Zhang, D., Yu, K., Yin, P., Cao, Y., Deng, W., Xu, K., Li, W."α‑hederin overcomes hypoxia‑mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway". International Journal of Oncology 62.3 (2023): 33.
Chicago
Chen, J., Xu, J., Yang, J., Zhan, Y., Li, S., Jia, L., Wu, W., Si, X., Zhang, D., Yu, K., Yin, P., Cao, Y., Deng, W., Xu, K., Li, W."α‑hederin overcomes hypoxia‑mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway". International Journal of Oncology 62, no. 3 (2023): 33. https://doi.org/10.3892/ijo.2023.5481