目的 考察木犀草素抗胃癌增殖和转移的作用及机制。方法 采用含10% FBS的RPMI-1640培养基培养BGC-823和MGC-803胃癌细胞;通过MTT实验考察不同浓度木犀草素(10、20、40 μmol·L-1)对胃癌细胞增殖活力的影响;采用划痕实验考察不同浓度木犀草素对胃癌细胞迁移能力的影响;采用Western blot考察木犀草素对增殖相关蛋白、EMT相关蛋白以及缺氧诱导因子(hypoxia-inducible factor 1α,HIF-1α)表达的影响;采用实时荧光定量聚合酶链式反应(real time PCR,RT-PCR)考察木犀草素对HIF-1α mRNA表达的影响;采用siRNA敲减HIF-1α,考察HIF-1α对木犀草素抗胃癌细胞增殖和迁移的影响。结果 木犀草素浓度依赖和时间依赖性地抑制BGC-823、MGC-803胃癌细胞的增殖和迁移;木犀草素抑制p-AKT、p-mTOR、p-p70S6k、N-cadherin、Vimentin的表达,促进E-cadherin的表达;木犀草素在mRNA和蛋白水平浓度依赖性地抑制HIF-1α的表达,敲减HIF-1α减弱木犀草素抗BGC-823、MGC-803胃癌细胞增殖和迁移的能力。结论 木犀草素可通过HIF-1α抗胃癌细胞增殖和迁移。
Abstract
OBJECTIVE To investigate the effect of luteolin on the proliferation and metastasis of gastric cancer and its mechanism. METHODS BGC-823 and MGC-803 gastric cancer cells were cultured with RPMI 1640 medium containing 10% FBS. MTT assay was used to investigate the effect of different concentrations of luteolin (10, 20, 40 μmol·L-1) on the proliferation activity of gastric cancer cells. The effect of different concentrations of luteolin on the migration ability of gastric cancer cells was investigated by scratch experiment. Western blot was used to investigate the effect of luteolin on the expression of proliferation-related proteins, EMT-related proteins and HIF-1α. The effect of luteolin on HIF-1α mRNA expression was investigated by RT-PCR. siRNA knockdown of HIF-1α was used to investigate the effect of HIF-1α on the proliferation and migration of luteolin against gastric cancer cells. RESULTS The proliferation and migration of BGC-823 and MGC-803 gastric cancer cells were inhibited by luteolin in a concentration and time dependent manner. Luteolin inhibited the expression of p-AKT, p-mTOR, p-p70S6k, N-cadherin and vimentin and promoted E-cadherin expression. Luteolin inhibited the expression of HIF-1α in a dosage dependent manner at both mRNA and protein levels. HIF-1α knockdown weakened the ability of luteolin to resist the proliferation and migration of BGC-823 and MGC-803 gastric cancer cells. CONCLUSION Luteolin can inhibit the proliferation and metastasis of gastric cancer cells by inhibiting HIF-1α.
关键词
木犀草素 /
胃癌 /
增殖 /
迁移 /
缺氧诱导因子1α
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Key words
luteolin /
gastric cancer /
proliferation /
migration /
HIF-1α
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中图分类号：
R969.1
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参考文献
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