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茯苓酸调控PI3K/AKT/mTOR通路介导葡萄糖代谢促进结直肠癌细胞凋亡的机制研究

Mechanism of Pachymic Acid Regulating PI3K/AKT/mTOR Pathway to Mediate Glucose Metabolism and Promote Colorectal Cancer Cell Apoptosis
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摘要 目的 研究茯苓酸对结直肠癌细胞葡萄糖代谢及细胞凋亡的调控作用。方法 通过细胞活性测定(Cell Counting Kit-8,CCK8)、克隆形成等实验检测茯苓酸对结直肠癌细胞增殖与细胞活性的影响;采用Annexin V-FITC/PI双染流式细胞凋亡实验检测茯苓酸对结直肠癌细胞凋亡的影响;使用细胞氧气消耗率和细胞外酸化率测定仪器及细胞葡萄糖代谢水平测定试剂盒检测茯苓酸对结直肠癌细胞葡萄糖代谢的影响;通过蛋白免疫印迹(Western blotting, WB)实验验证凋亡、糖酵解、磷脂酰肌醇3-激酶(Phosphatidylinositol3-kinase, PI3K)/丝氨酸、苏氨酸蛋白激酶(AKT Serine/Threonine Kinase 1,AKT)/雷帕霉素靶蛋白(Mammalian Target of Rapamycin, mTOR)通路相关蛋白表达情况。结果 茯苓酸能够有效抑制结直肠癌细胞增殖与细胞活性,并能够通过抑制其糖酵解水平促进其细胞凋亡,同时显著抑制PI3K/AKT/mTOR通路相关蛋白表达水平。结论 茯苓酸可通过调控PI3K/AKT/mTOR通路介导葡萄糖代谢促进CRC细胞凋亡,可作为未来结直肠癌代谢靶向治疗的潜在药物。 Objective To study the effect of pachymic acid on glucose metabolism and apoptosis in colorectal cancer cells.Methods The effects of pachymic acid on the proliferation and cell activity of colorectal cancer cells were detected by CCK8,clone formation and other experiments.Annexin V-FITC/PI double staining flow cytometry was used to detect the effect of pachymic acid on apoptosis of colorectal cancer cells.The effects of pachymic acid on glucose metabolism of colorectal cancer cells were detected by cell oxygen consumption rate,extracellular acidification rate and cell glucose metabolism test kit.The expressions of proteins related to apoptosis,glycolysis and phosphatidylinositol 3-kinase(PI3K)/threonine kinase 1(AKT)/mammalian target of rapamycin(mTOR)pathway were verified by Western blot.Results Pachymic acid could effectively inhibit the proliferation and cell activity of colorectal cancer cells,promote the apoptosis by inhibiting the glycolysis level and significantly inhibit the expressions of PI3K/AKT/mTOR pathway related proteins.Conclusion Pachymic acid can promote CRC cell apoptosis by regula-ting glucose metabolism mediated by PI3K/AKT/mTOR pathway,which can be used as a potential drug for metabolic therapy of colorectal cancer in the future.
作者 张树瑛 石齐 殷晓聆 侯风刚 ZHANG Shuying;SHI Qi;YIN Xiaoling;HOU Fenggang(Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China)
出处 《中华中医药学刊》 CAS 北大核心 2024年第9期65-69,I0008,I0009,共7页 Chinese Archives of Traditional Chinese Medicine
基金 国家自然科学基金项目(82174188) 国家中医药管理局第五批全国中医临床优秀人才项目(R221127N) 上海市中医医院“未来计划”项目(WLJH2021ZY-MZY024)。
关键词 茯苓酸 结直肠癌 糖酵解 细胞凋亡 PI3K/AKT/mTOR信号通路 pachymic acid colorectal cancer glycolysis cell apoptosis PI3K/AKT/mTOR signaling pathway
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