Harmine induces apoptosis and inhibits tumor cell proliferation, migration and invasion through down-regulation of cyclooxygenase-2 expression in gastric cancer
Harmine induces apoptosis and inhibits tumor cell proliferation, migration and invasion through down-regulation of cyclooxygenase-2 expression in gastric cancer
复制标题
骆驼蓬碱通过下调胃癌中环氧合酶2表达诱导细胞凋亡并抑制肿瘤细胞增殖、迁移和侵袭
DOI：
10.1016/j.phymed.2013.09.007
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发表时间：
2014-02-15
期刊：
影响因子：
7.9
通讯作者：
Sun, Weihao
中科院分区：
文献类型：
--
作者：
Zhang, Hao;Sun, Kun;Sun, Weihao
环氧合酶-2(COX-2)在胃癌的发生发展中起重要作用。骆驼蓬碱被认为是一种很有前途的治疗癌症的候选药物，然而，骆驼蓬碱对人胃癌细胞的作用和作用机制尚不清楚。本研究评价了骆驼蓬碱在体内外对人胃癌的抗肿瘤作用。用四甲基偶氮唑盐比色法测定细胞增殖。用DAPI染色和流式细胞仪分析细胞凋亡率。通过创面愈合和跨孔侵袭实验评价三尖杉酯碱对胃癌细胞迁移和侵袭的影响。免疫印迹法检测COX-2、增殖细胞核抗原(PCNA)、Bcl2、Bax和基质金属蛋白酶-2(MMP2)的表达。结果表明，骆驼蓬碱在体外能显著抑制细胞的增殖、迁移、侵袭和诱导细胞凋亡，并能抑制体内肿瘤的生长。此外，骆驼蓬碱还能显著抑制胃癌细胞中COX-2、PCNA、Bcl2和MMP2的表达，上调Bax的表达。以上结果提示，骆驼蓬碱可诱导人胃癌细胞凋亡，抑制其增殖、迁移和侵袭，其机制可能与下调COX-2的表达有关。(C)2013年爱思唯尔股份有限公司。版权所有。
Cyclooxygenase-2 (COX-2) plays an important role in the carcinogenesis and progression of gastric cancer. Harmine is reported as a promising drug candidate for cancer therapy; however, effects and action mechanism of harmine on the human gastric cancer cells remain unclear. This study evaluated the anti-tumor effects of harmine on human gastric cancer both in vitro and in vivo. The cell proliferation was determined using MTT colorimetric assay. Apoptosis was measured by DAPI staining and flow cytometry analysis. The wound healing and transwell invasion assays were performed to evaluate the effects of harmine on the migration and invasion of gastric cancer cells. The expression of COX-2, proliferating cell nuclear antigen (PCNA), Bcl-2, Bax and matrix metalloproteinase-2 (MMP-2) was detected by Western blot analysis. Our results showed that harmine significantly inhibited cellular proliferation, migration, invasion and induced apoptosis in vitro, as well as inhibited tumor growth in vivo. In addition, harmine significantly inhibited the expression of COX-2, PCNA, Bcl-2 and MMP-2 as well as increased Bax expression in gastric cancer cells. These results collectively indicate that harmine induces apoptosis and inhibits proliferation, migration and invasion of human gastric cancer cells, which may be mediated by down-regulation of COX-2 expression. (C) 2013 Elsevier GmbH. All rights reserved.