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Background <p>Gemcitabine (GEM)-based chemotherapy is essential for treating recurrent or metastatic nasopharyngeal carcinoma (NPC). However, the limited sensitivity, coupled with the associated toxicities and side effects, hinder its overall efficacy. Orlistat (Orli), a US FDA-approved weight loss drug and fatty acid synthase (FASN) inhibitor, can slow NPC progression and improve treatment outcomes, but these effects are largely unstudied.</p> Methods <p>The cell counting kit-8 (CCK-8) assay, colony formation assay, scratch wound healing assay, glucose uptake assay, online soft SynergyFinder analysis and xenograft assay were conducted to evaluate the effect of Orli combined with GEM on NPC inhibition in vitro and in vivo. Additionally, lentivirus transfection, and bioinformatics analyses were employed to explore the underlying mechanisms.</p> Results <p>In vitro experiment revealed that Orli inhibited cell proliferation, colony-formation, glycolysis and migration ability of NPC while also demonstrating a synergistic effect when combined with the chemotherapeutic agent GEM. Mechanistically, the data showed that Orli significantly reduced pyruvate kinase M2(PKM2) expression, which significantly suppressed NPC cell proliferation and migration, thereby enhancing the therapeutic effect of GEM both in vitro and in vivo.</p> Conclusions <p>Oril may serve as a promising chemosensitizer in conjunction with GEM to improve the prognosis of patients with NPC.</p>

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Orlistat potentiates the gemcitabine effect in inhibiting the malignant biological behavior of nasopharyngeal carcinoma by downregulating PKM2

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月13日

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  • Peishan Zhang,
  • Qinfang Cai,
  • Shaoji Ouyang

摘要

Background

Gemcitabine (GEM)-based chemotherapy is essential for treating recurrent or metastatic nasopharyngeal carcinoma (NPC). However, the limited sensitivity, coupled with the associated toxicities and side effects, hinder its overall efficacy. Orlistat (Orli), a US FDA-approved weight loss drug and fatty acid synthase (FASN) inhibitor, can slow NPC progression and improve treatment outcomes, but these effects are largely unstudied.

Methods

The cell counting kit-8 (CCK-8) assay, colony formation assay, scratch wound healing assay, glucose uptake assay, online soft SynergyFinder analysis and xenograft assay were conducted to evaluate the effect of Orli combined with GEM on NPC inhibition in vitro and in vivo. Additionally, lentivirus transfection, and bioinformatics analyses were employed to explore the underlying mechanisms.

Results

In vitro experiment revealed that Orli inhibited cell proliferation, colony-formation, glycolysis and migration ability of NPC while also demonstrating a synergistic effect when combined with the chemotherapeutic agent GEM. Mechanistically, the data showed that Orli significantly reduced pyruvate kinase M2(PKM2) expression, which significantly suppressed NPC cell proliferation and migration, thereby enhancing the therapeutic effect of GEM both in vitro and in vivo.

Conclusions

Oril may serve as a promising chemosensitizer in conjunction with GEM to improve the prognosis of patients with NPC.