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Andrographolide acts with dexamethasone to inhibit the growth of acute lymphoblastic leukemia CEM‑C1 cells via the regulation of the autophagy‑dependent PI3K/AKT/mTOR signaling pathway

  • Authors:
    • Xiaowen Li
    • Tong Wu
    • Weihong Chen
    • Jiannan Zhang
    • Yanping Jiang
    • Jianzhi Deng
    • Wenqing Long
    • Xi Qin
    • Yuehan Zhou

  • View Affiliations

  • Published online on: January 19, 2024     https://doi.org/10.3892/br.2024.1731
  • Article Number: 43

  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute lymphoblastic leukemia (ALL) is one of the most common malignant tumor types of the circulatory system. Dexamethasone (DEX) acts on the glucocorticoid (GC) receptor (GR) and is a first‑line chemotherapy drug for ALL. However, long‑term or high‑dose applications of the drug can not only cause adverse reactions, such as osteoporosis and high blood pressure, but can also cause downregulation of GR and lead to drug resistance. In the present study, reverse transcription‑quantitative PCR, western blotting and LysoTracker Red staining were used to observe the effects of DEX and andrographolide (AND; a botanical with antitumorigenic properties) combined treatment. It was found that AND enhanced the sensitivity of CEM‑C1 cells, a GC‑resistant cell line, to DEX, and synergistically upregulated GR both at the transcriptional and post‑transcriptional level with DEX. The combination of AND with DEX synergistically alkalized lysosomal lumen and downregulated the expression of autophagy‑related genes Beclin1 and microtubule‑associated 1 protein light chain 3 (LC3), thereby inhibiting autophagy. Knocking down LC3 expression enhanced GR expression, suggesting that GR was regulated by autophagy. Furthermore, compared with the monotherapy group (AND or DEX in isolation), AND interacted with DEX to activate the autophagy‑dependent PI3K/AKT/mTOR signaling pathway by enhancing the phosphorylation of PI3K, AKT and mTOR, thereby decreasing GR degradation and increasing the sensitivity of cells to GCs. In conclusion, the present study demonstrated that AND exhibited a synergistic anti‑ALL effect with DEX via upregulation of GR, which was orchestrated by the autophagy‑related PI3K/AKT/mTOR signaling pathway. The results of the present study therefore provided novel research avenues and strategies for the treatment of ALL.
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March-2024
Volume 20 Issue 3

Print ISSN: 2049-9434
Online ISSN:2049-9442

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Spandidos Publications style
Li X, Wu T, Chen W, Zhang J, Jiang Y, Deng J, Long W, Qin X and Zhou Y: Andrographolide acts with dexamethasone to inhibit the growth of acute lymphoblastic leukemia CEM‑C1 cells via the regulation of the autophagy‑dependent PI3K/AKT/mTOR signaling pathway. Biomed Rep 20: 43, 2024.
APA
Li, X., Wu, T., Chen, W., Zhang, J., Jiang, Y., Deng, J. ... Zhou, Y. (2024). Andrographolide acts with dexamethasone to inhibit the growth of acute lymphoblastic leukemia CEM‑C1 cells via the regulation of the autophagy‑dependent PI3K/AKT/mTOR signaling pathway. Biomedical Reports, 20, 43. https://doi.org/10.3892/br.2024.1731
MLA
Li, X., Wu, T., Chen, W., Zhang, J., Jiang, Y., Deng, J., Long, W., Qin, X., Zhou, Y."Andrographolide acts with dexamethasone to inhibit the growth of acute lymphoblastic leukemia CEM‑C1 cells via the regulation of the autophagy‑dependent PI3K/AKT/mTOR signaling pathway". Biomedical Reports 20.3 (2024): 43.
Chicago
Li, X., Wu, T., Chen, W., Zhang, J., Jiang, Y., Deng, J., Long, W., Qin, X., Zhou, Y."Andrographolide acts with dexamethasone to inhibit the growth of acute lymphoblastic leukemia CEM‑C1 cells via the regulation of the autophagy‑dependent PI3K/AKT/mTOR signaling pathway". Biomedical Reports 20, no. 3 (2024): 43. https://doi.org/10.3892/br.2024.1731