目的 探讨牛蒡子苷元(ARG)对胃癌细胞增殖、迁移和侵袭的影响及可能的作用机制。方法 体外培养胃癌BGC-823细胞,分别采用不同浓度(10、20和40 mg·L-1)的ARG干预24 h、转染si-SETDB1以及转染pcDNA-SETDB1和40 mg·L-1的ARG共同作用胃癌BGC-823细胞,四甲基偶氮唑蓝(MTT)法检测胃癌BGC-823细胞增殖,Transwell法检测胃癌BGC-823细胞迁移和侵袭能力,Western blot法检测胃癌BGC-823细胞增殖、迁移、侵袭相关蛋白和SETDB1蛋白表达,qRT-PCR检测SETDB1 mRNA表达。结果 ARG干预胃癌BGC-823细胞24 h和转染si-SETDB1均能增加胃癌BGC-823细胞增殖的抑制率,减少BGC-823细胞迁移和侵袭数量,下调cyclin D1、基质金属蛋白酶(MMP)-2、MMP-9和MMP-14蛋白表达,上调p21和p27蛋白表达明显,下调SETDB1 mRNA和蛋白表达。SETDB1过表达逆转了ARG对胃癌BGC-823细胞增殖、迁移和侵袭的作用及相关蛋白cyclin D1、p21、MMP-2和MMP-9的影响。结论 ARG可能通过调控SETDB1表达抑制胃癌BGC-823细胞的增殖、迁移和侵袭。
Abstract
OBJECTIVE To investigate the effects of arctigenin (ARG) on the proliferation, migration and invasion of gastric cancer cells and its possible mechanism. METHODS BGC-823 cells were cultured in vitro, and cells were treated with ARG at different concentrations (10, 20, 40 mg·L-1) for 24 h, transfected with si-SETDB1, and transfected with pcDNA-SETDB1 and 40 mg·L-1 ARG. The proliferation of gastric cancer BGC-823 cells was detected by MTT assay. The migration and invasion ability were detected by Transwell method. The proteins associated with proliferation, migration and invasion and SETDB1 protein were detected by Western blot. SETDB1 mRNA expression was detected by qRT-PCR. RESULTS ARG and transfected si-SETDB1 could inhibit the proliferation of gastric cancer BGC-823 cells, decrease the migration and invasion of BGC-823 cells, down-regulate the expression of cyclin D1, MMP-2, MMP-9 and MMP-14 protein,and up-regulate the expression of p21 and p27 protein.The expression of SETDB1 mRNA and protein were down-regulated. Overexpression of SETDB1 reversed the effects of ARG on proliferation, migration and invasion of gastric cancer BGC-823 cells and the related proteins cyclin D1, p21, MMP-2 and MMP-9. CONCLUSION ARG may inhibit the proliferation, migration and invasion of gastric cancer BGC-823 cells by regulating the expression of SETDB1.
关键词
牛蒡子苷元 /
胃癌 /
SETDB1 /
增殖 /
迁移 /
侵袭
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Key words
arctigenin /
gastric cancer /
SETDB1 /
proliferation /
migration /
invasion
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中图分类号：
R965
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脚注
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基金
国家自然科学基金面上项目资助(81472714)
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