Berberine enhances inhibition of glioma tumor cell migration and invasiveness mediated by arsenic trioxide.
Berberine enhances inhibition of glioma tumor cell migration and invasiveness mediated by arsenic trioxide.
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DOI：
10.1186/1471-2407-8-58
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发表时间：
2008-02-25
期刊：
影响因子：
3.8
通讯作者：
Lu, Fung-Jou
中科院分区：
文献类型：
--
作者：
Lin, Tseng-Hsi;Kuo, Hsing-Chun;Chou, Fen-Pi;Lu, Fung-Jou
三氧化二砷（As 2 O3）在急性早幼粒细胞白血病患者中显示出良好的抗癌活性，并在体外诱导多种肿瘤细胞凋亡。在这里，我们研究了天然生物碱小檗碱对As 2 O3介导的抑制癌细胞迁移的大鼠和人类胶质瘤细胞系的影响。采用MTT法检测As 2 O3、小檗碱及As 2 O3与小檗碱联合作用后大鼠C6和人U-87胶质瘤细胞的存活率。采用划痕法和Boyden小室法检测As 2 O3和小檗碱对胶质瘤细胞迁移能力和侵袭能力的影响。酶谱和Western blot分析提供了As 2 O3和小檗碱对蛋白激酶C（PKC）胞内转位和激活的影响，以及一些PKC相关的下游因子的信息。大多数试验独立进行三次，并使用ANOVA分析数据。细胞活力的研究表明，小檗碱增强As 2 O3介导的抑制胶质瘤细胞生长后，24小时孵育。未处理的对照细胞形成汇合层，其形成在用5 μM As 2 O3孵育后受到抑制。在存在10 μM小檗碱的情况下，后一种效应甚至更明显。与小檗碱共同处理后，As 2 O3介导的胶质瘤细胞运动和侵袭能力的降低得到增强。此外，据报道，PKC亚型影响肌动蛋白细胞骨架的形态，以及金属蛋白酶MT 1-MMP和MMP-2的活化，据报道参与癌细胞迁移。As 2 O3和小檗碱处理胶质瘤细胞后，PKC α和ε的活化明显降低，肌动蛋白骨架发生重排。两个下游转录因子myc和jun以及MT 1-MMP和MMP-2的水平也显著降低。当用As 2 O3和小檗碱共同处理胶质瘤细胞时，癌细胞转移可以被显著抑制，最有可能是通过阻断参与癌细胞迁移的PKC介导的信号通路。这项研究是潜在的兴趣，在恶性胶质瘤和癌症发展的治疗新的化疗方法的发展。
Arsenic trioxide (As2O3) exhibits promising anticarcinogenic activity in acute promyelocytic leukemic patients and induces apoptosis in various tumor cells in vitro. Here, we investigated the effect of the natural alkaloid berberine on As2O3-mediated inhibition of cancer cell migration using rat and human glioma cell lines. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine the viability of rat C6 and human U-87 glioma cells after treatment with As2O3 or berberine, and after co-treatment with As2O3 and berberine. The wound scratch and Boyden chamber assays were applied to determine the effect of As2O3 and berberine on the migration capacity and invasiveness of glioma cancer cells. Zymography and Western blot analyses provided information on the effect of As2O3 and berberine on the intracellular translocation and activation of protein kinase C (PKC), and some PKC-related downstream factors. Most assays were performed three times, independently, and data were analyzed using ANOVA. The cell viability studies demonstrated that berberine enhances As2O3-mediated inhibition of glioma cell growth after 24 h incubation. Untreated control cells formed a confluent layer, the formation of which was inhibited upon incubation with 5 μM As2O3. The latter effect was even more pronounced in the presence of 10 μM berberine. The As2O3-mediated reduction in motility and invasion of glioma cells was enhanced upon co-treatment with berberine. Furthermore, it has been reported that PKC isoforms influence the morphology of the actin cytoskeleton, as well as the activation of metalloproteases MT1-MMP and MMP-2, reported to be involved in cancer cell migration. Treatment of glioma cells with As2O3 and berberine significantly decreased the activation of PKC α and ε and led to actin cytoskeleton rearrangements. The levels of two downstream transcription factors, myc and jun, and MT1-MMP and MMP-2 were also significantly reduced. Upon co-treatment of glioma cells with As2O3 and berberine, cancer cell metastasis can be significantly inhibited, most likely by blocking the PKC-mediated signaling pathway involved in cancer cell migration. This study is potentially interesting for the development of novel chemotherapeutic approaches in the treatment of malignant gliomas and cancer development in general.
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影响因子：
3.6
作者：
Chen, Z;Chen, GQ;Chen, SJ
通讯作者：
Chen, SJ
影响因子：
9.7
作者：
Cheung, William M. W.;Chu, Patrick W. K.;Kwong, Yok L.
通讯作者：
Kwong, Yok L.
影响因子：
10.4
作者：
Dong, ZG
通讯作者：
Dong, ZG
影响因子：
11.2
作者：
Koivunen, J;Aaltonen, V;Peltonen, J
通讯作者：
Peltonen, J
DOI：
10.1016/s0736-5748(99)00054-4
发表时间：
1999-08-01
影响因子：
1.8
作者：
Cho, KK;Mikkelsen, T;Rosenblum, ML
通讯作者：
Rosenblum, ML