Scholarlink

<p>This study examined whether bempedoic acid (BPA) suppresses SEC progression through an integrated pharmacological framework with toxicological relevance, targeting metabolic, inflammatory, oxidative, angiogenic, proliferative, and apoptotic pathways. Fifty female Swiss albino mice were assigned to five groups (<i>n</i> = 10): normal control, untreated SEC control, SEC + bempedoic acid (10 or 30&#xa0;mg/kg, orally), and SEC + doxorubicin (5&#xa0;mg/kg, i.p.) three times weekly for two weeks as a reference chemotherapeutic comparator with established clinical toxicity relevance. After experiment completion, blood and tumor tissues were obtained for molecular assessment. SEC-bearing mice showed lipid dysregulation, with elevated ACLY, ACC, FASN, total cholesterol, and triglycerides, alongside suppressed AMPK. BPA counteracted these changes by inhibiting ACLY-driven lipogenesis and restoring AMPK-related signaling, thereby reducing NF-κB pathway activity and iNOS, IL-6, and TNF-α. It also attenuated oxidative stress, increasing SOD and lowering p-carbonyls. Moreover, BPA reduced VEGF, MMP-2, MMP-9, Hes-1, DLL4, Notch-1, and Jagged-1, indicating impaired angiogenic remodeling and endothelial differentiation. Decreased Cyclin-D1 and PCNA reflected reduced proliferation, while increased p53, Bax, and Caspase-3 indicated enhanced apoptosis. Histologically, BPA promoted dose-dependent tumor necrosis, reduced viable anaplastic cell clusters, and induced fibrovascular granulation tissue with peripheral inflammatory cell infiltration, indicating tumor regression and reparative remodeling. These findings provide preclinical evidence that BPA reduces SEC tumor burden by modulating the ACLY/AMPK-related metabolic pathway, accompanied by suppression of inflammatory, angiogenic, proliferative, survival, oxidative stress, and apoptosis-related dysregulation, supporting its repurposing potential as a multi-target therapeutic candidate for solid tumors.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Modulation of the ACLY–AMPK axis by bempedoic acid suppresses NF-κB-driven inflammation, VEGF–Notch angiogenic crosstalk, and cell-cycle progression in Solid Ehrlich Carcinoma

  • 期刊论文

  • 发表日期：

    2026年7月3日

查看全文
  • Asmaa Saleh,
  • Nahed A. Raslan,
  • Heba Mohammed Refat M. Selim,
  • Ahmed Mohamed Farghly,
  • Sahar K. Ali,
  • Omneya Galal,
  • Bassant M. Barakat,
  • Reda M. Fayyad,
  • Samar H. Rizk,
  • Shaza M. Elhusseiny,
  • Amina Ibrahim Badawy,
  • Huda Mahmoud Fettouh Saadat,
  • Mai Ahmed Salem,
  • Ayman Salama,
  • Heba Abdelnaser Aboelsoud,
  • Mohammed Hegazy Hassan Ali,
  • Alaa A. A. Abd allatif,
  • Mohamed Fathy AbdElhamid Mohamed,
  • Safaa M. Hanafy,
  • Somia Mokabel Mohamed,
  • Asmaa Magdy Elashrey,
  • Sara Nagdy Mahmoud Mousa,
  • Wafaa Ibrahim Soliman,
  • Shimaa M. Motawei,
  • Ahmed M. El-Dessouki

摘要

This study examined whether bempedoic acid (BPA) suppresses SEC progression through an integrated pharmacological framework with toxicological relevance, targeting metabolic, inflammatory, oxidative, angiogenic, proliferative, and apoptotic pathways. Fifty female Swiss albino mice were assigned to five groups (n = 10): normal control, untreated SEC control, SEC + bempedoic acid (10 or 30 mg/kg, orally), and SEC + doxorubicin (5 mg/kg, i.p.) three times weekly for two weeks as a reference chemotherapeutic comparator with established clinical toxicity relevance. After experiment completion, blood and tumor tissues were obtained for molecular assessment. SEC-bearing mice showed lipid dysregulation, with elevated ACLY, ACC, FASN, total cholesterol, and triglycerides, alongside suppressed AMPK. BPA counteracted these changes by inhibiting ACLY-driven lipogenesis and restoring AMPK-related signaling, thereby reducing NF-κB pathway activity and iNOS, IL-6, and TNF-α. It also attenuated oxidative stress, increasing SOD and lowering p-carbonyls. Moreover, BPA reduced VEGF, MMP-2, MMP-9, Hes-1, DLL4, Notch-1, and Jagged-1, indicating impaired angiogenic remodeling and endothelial differentiation. Decreased Cyclin-D1 and PCNA reflected reduced proliferation, while increased p53, Bax, and Caspase-3 indicated enhanced apoptosis. Histologically, BPA promoted dose-dependent tumor necrosis, reduced viable anaplastic cell clusters, and induced fibrovascular granulation tissue with peripheral inflammatory cell infiltration, indicating tumor regression and reparative remodeling. These findings provide preclinical evidence that BPA reduces SEC tumor burden by modulating the ACLY/AMPK-related metabolic pathway, accompanied by suppression of inflammatory, angiogenic, proliferative, survival, oxidative stress, and apoptosis-related dysregulation, supporting its repurposing potential as a multi-target therapeutic candidate for solid tumors.