Coptis chinensis inhibits hepatocellular carcinoma cell growth through nonsteroidal anti-inflammatory drug-activated gene activation
Coptis chinensis inhibits hepatocellular carcinoma cell growth through nonsteroidal anti-inflammatory drug-activated gene activation
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DOI：
10.3892/ijmm_00000267
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发表时间：
2009-10-01
影响因子：
5.4
通讯作者：
Ko, Joshua Ka-Shun
中科院分区：
文献类型：
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作者：
Auyeung, Kathy Ka-Wai;Ko, Joshua Ka-Shun
肝癌的常规化疗不能提供令人满意的缓解，并可能导致严重的副作用，因此，获得具有已知作用机制的有效抑制癌细胞生长的替代治疗至关重要。在本研究中，我们研究了黄连及其主要成分小檗碱在HepG 2肝癌细胞中的抗癌作用，并试图阐明其潜在的机制，包括参与非甾体抗炎药（NSAID）激活基因（NAG-1）。黄连或小檗碱可抑制HepG 2细胞增殖、诱导细胞凋亡并使细胞周期阻滞在G2/M期。促凋亡作用与Bcl-2的相应下调、半胱氨酸天冬氨酸蛋白酶原-3和-9的活化以及聚（ADP-核糖）聚合酶的裂解相关。我们进一步证明了NAG-1参与了其上游转录因子早期生长反应基因（Egr-1）激活后的促凋亡事件。这通过在Egr-1/DNA结合活性升高之前增加NAG-1启动子活性来证实。我们的研究结果表明，黄连和小檗碱都是潜在的抗癌药物在治疗肝癌诱导细胞周期阻滞和促进凋亡，而NAG-1是在药物诱导的HepG 2细胞凋亡的作用过程中的分子靶点。
Conventional chemotherapy of liver cancer fails to provide satisfactory remission and may cause serious side effects, thus it is crucial to derive alternative treatments that effectively inhibit cancer cell growth with known mechanisms of action. In the present study, we investigated the anti-carcinogenic effects of Coptis chinensis and its major constituent, berberine, in HepG2 hepatocellular carcinoma (HCC) cells and attempted to elucidate the underlying mechanism, including involvement of the nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1). Inhibition of cell proliferation, induction of apoptosis and cell cycle arrest at the G2/M phase were observed in HepG2 cells treated with Coptis chinensis or berberine. The pro-apoptotic effects were associated with corresponding down-regulation of Bcl-2, activation of procaspase-3 and -9 as well as cleavage of poly (ADP-ribose) polymerase. We further demonstrated the involvement of NAG-1 in the pro-apoptotic events following prior activation of its upstream transcriptional factor early growth response gene (Egr-1). This was confirmed by increased NAG-1 promoter activity preceded by the elevation of Egr-1/DNA binding activity. Our results suggest that both Coptis chinensis and berberine are potential anti-carcinogenic agents in treating HCC by inducing cell cycle arrest and promotion of apoptosis, while NAG-1 is a molecular target during the drug-induced pro-apoptotic action in HepG2 cells.