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<p> Chemotherapy failure caused by adriamycin (ADM) and imatinib (IM) resistance remains a critical challenge in the treatment of chronic myeloid leukemia (CML). In this study, a novel compound 4, 4’-(selenophene-2, 5-diyl)bis(3-fluorophenol) (<b>Se-1</b>) with estrogen receptor regulation and selenium anticancer activity was applied to reverse drug resistance of CML. <b>Se-1</b> exhibited superior inhibitory activity against resistant K562/ADM cells compared to sensitive K562 cells. The growth of K562/ADM in xenograft mouse was suppressed by <b>Se-1</b> treatment. The anti-leukemia mechanism of <b>Se-1</b> was tested by western-blot, flow cytometry, molecular docking and fluorescence imaging. The apoptosis rate was increasing after <b>Se-1</b> treatment, meanwhile proteins of Cleaved PARP and Cleaved Caspase3 were up-regulated and Bcl-2 was down-regulated. In addition, the autophagy was activated through increasing of autophagy vesicles and proteins of LC3-II and P62, and inactivating of mTOR protein. Moreover, estrogen receptor α (ERα), ERK and P38 were activated, the proteins of PI3K and AKT1 were decreased. Overall, <b>Se-1</b> exerted anti-CML effects through multi-mechanism interaction, which was expected to advance the research in reversing ADM and IM resistance of chronic myeloid leukemia.</p>

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A selenium-containing selective estrogen receptor modulator to overcome drug resistance of chronic myeloid leukemia

  • 期刊论文

  • 发表日期：

    2026年1月10日

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  • Jing Liu,
  • Chunmei Yang,
  • Didi Gu,
  • Ling Guo,
  • Yan Zeng,
  • Qulian Guo,
  • You Yang,
  • Qiuyu Meng,
  • Jian Shu,
  • Wenjun Liu,
  • Lu Yang

摘要

Chemotherapy failure caused by adriamycin (ADM) and imatinib (IM) resistance remains a critical challenge in the treatment of chronic myeloid leukemia (CML). In this study, a novel compound 4, 4’-(selenophene-2, 5-diyl)bis(3-fluorophenol) (Se-1) with estrogen receptor regulation and selenium anticancer activity was applied to reverse drug resistance of CML. Se-1 exhibited superior inhibitory activity against resistant K562/ADM cells compared to sensitive K562 cells. The growth of K562/ADM in xenograft mouse was suppressed by Se-1 treatment. The anti-leukemia mechanism of Se-1 was tested by western-blot, flow cytometry, molecular docking and fluorescence imaging. The apoptosis rate was increasing after Se-1 treatment, meanwhile proteins of Cleaved PARP and Cleaved Caspase3 were up-regulated and Bcl-2 was down-regulated. In addition, the autophagy was activated through increasing of autophagy vesicles and proteins of LC3-II and P62, and inactivating of mTOR protein. Moreover, estrogen receptor α (ERα), ERK and P38 were activated, the proteins of PI3K and AKT1 were decreased. Overall, Se-1 exerted anti-CML effects through multi-mechanism interaction, which was expected to advance the research in reversing ADM and IM resistance of chronic myeloid leukemia.