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Background <p>We aimed to characterise the molecular effects of treating myelodysplastic syndrome (MDS) cells with the DNA methyltransferase inhibitor azacitidine and an PIM-2 inhibitor, focusing on their potential synergistic effects.</p> Methods <p>MDS cells were subjected to proliferation assays to assess the effects of each drug independently and in combination. The synergy of the drugs in promoting the apoptosis of MDS cells via NF-κB signalling pathway inhibition was evaluated.</p> Results <p>Our results suggested that azacitidine and the PIM-2 inhibitor have synergistic effects in inhibiting the proliferation and inducing the apoptosis of MDS cells. Furthermore, the combined application of azacitidine and PIM-2 inhibitor synergistically inhibited the NF-κB pathway, resulting in the induction of apoptosis in MDS cells.</p> Conclusion <p>Administration of a small molecule PIM-2 inhibitor in combination with the epigenetic drug azacitidine is one of the effective ways to treat MDS. Our study lays a foundation for future clinical trials in patients with MDS.</p> Graphical abstract <p></p>

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Synergistic apoptosis induction in myelodysplastic syndrome cells by azacitidine and PIM-2 inhibitors via nuclear factor-kappa B pathway inhibition

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月21日

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  • Yixuan Guo,
  • Zhaoyun Liu,
  • Wenhui Lei,
  • Xiaohan Liu,
  • Chun Yang,
  • Kai Ding,
  • Rong Fu

摘要

Background

We aimed to characterise the molecular effects of treating myelodysplastic syndrome (MDS) cells with the DNA methyltransferase inhibitor azacitidine and an PIM-2 inhibitor, focusing on their potential synergistic effects.

Methods

MDS cells were subjected to proliferation assays to assess the effects of each drug independently and in combination. The synergy of the drugs in promoting the apoptosis of MDS cells via NF-κB signalling pathway inhibition was evaluated.

Results

Our results suggested that azacitidine and the PIM-2 inhibitor have synergistic effects in inhibiting the proliferation and inducing the apoptosis of MDS cells. Furthermore, the combined application of azacitidine and PIM-2 inhibitor synergistically inhibited the NF-κB pathway, resulting in the induction of apoptosis in MDS cells.

Conclusion

Administration of a small molecule PIM-2 inhibitor in combination with the epigenetic drug azacitidine is one of the effective ways to treat MDS. Our study lays a foundation for future clinical trials in patients with MDS.

Graphical abstract