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Background <p>Irinotecan (CPT-11) is a standard first-line chemotherapy treatment for colorectal cancer (CRC). However, its clinical application is often comprised by gastrointestinal toxicity and limited therapeutic efficacy. Our previous study has revealed that the combination of Vardenafil (Vard) and Linagliptin (Linag) significantly alleviated CPT-11-induced intestinal toxicity in both <i>in vitro</i> and <i>in vivo</i> models. It remains unclear whether this combination can synergistically enhance the anticancer activity of CPT-11.</p> Methods <p>The <i>in vitro</i> synergism of Vard, Linag, and CPT-11 was assessed using cell viability assays on CRC cell lines, including HCT116, SW620, and HT29. An <i>in vivo</i> xenograft mouse model was established to evaluate the drug efficacy of both the original and liposomal forms of Vard and Linag combined with CPT-11. Additionally, untargeted metabolomics was utilized to explore the potential mechanisms underlying the observed synergistic effects.</p> Results <p><i>In vitro</i>, the combination of Vard and Linag synergistically enhanced the anticancer activity of CPT-11 in CRC cell lines. <i>In vivo</i>, liposomal formulations of Vard and Linag tended to accumulate at the tumor site, improving drug targeting and synergistically enhancing the anticancer efficacy of CPT-11. Untargeted metabolomics analysis revealed that this synergistic effect was probably mediated through the regulation of lysophospholipid metabolism.</p> Conclusion <p>Liposomal Vard and Linag combined with CPT-11 demonstrated a synergistic anti-CRC effect, offering valuable insights into novel combination therapies in CRC treatment.</p> Graphical Abstract <p></p>

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Liposomal Vardenafil and Linagliptin Combined with Irinotecan for Synergistic Colorectal Cancer Therapy

  • 期刊论文

  • 发表日期：

    2025年6月5日

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  • Xian Zhao,
  • Ruijie Xu,
  • Yuanyuan Zhai,
  • Yi Wang,
  • Yuxin Zhang,
  • Yuan Tian,
  • Fengguo Xu,
  • Pei Zhang

摘要

Background

Irinotecan (CPT-11) is a standard first-line chemotherapy treatment for colorectal cancer (CRC). However, its clinical application is often comprised by gastrointestinal toxicity and limited therapeutic efficacy. Our previous study has revealed that the combination of Vardenafil (Vard) and Linagliptin (Linag) significantly alleviated CPT-11-induced intestinal toxicity in both in vitro and in vivo models. It remains unclear whether this combination can synergistically enhance the anticancer activity of CPT-11.

Methods

The in vitro synergism of Vard, Linag, and CPT-11 was assessed using cell viability assays on CRC cell lines, including HCT116, SW620, and HT29. An in vivo xenograft mouse model was established to evaluate the drug efficacy of both the original and liposomal forms of Vard and Linag combined with CPT-11. Additionally, untargeted metabolomics was utilized to explore the potential mechanisms underlying the observed synergistic effects.

Results

In vitro, the combination of Vard and Linag synergistically enhanced the anticancer activity of CPT-11 in CRC cell lines. In vivo, liposomal formulations of Vard and Linag tended to accumulate at the tumor site, improving drug targeting and synergistically enhancing the anticancer efficacy of CPT-11. Untargeted metabolomics analysis revealed that this synergistic effect was probably mediated through the regulation of lysophospholipid metabolism.

Conclusion

Liposomal Vard and Linag combined with CPT-11 demonstrated a synergistic anti-CRC effect, offering valuable insights into novel combination therapies in CRC treatment.

Graphical Abstract