Bidirectional functions of arsenic as a carcinogen and an anti-cancer agent in human squamous cell carcinoma.
Bidirectional functions of arsenic as a carcinogen and an anti-cancer agent in human squamous cell carcinoma.
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DOI：
10.1371/journal.pone.0096945
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kato M
中科院分区：
文献类型：
--
作者：
Thang ND;Yajima I;Kumasaka MY;Kato M
砷对癌细胞的双向促癌和抗癌作用已在以往的研究中被揭示。然而，在不同的砷处理浓度下，在不同的细胞中发现了每一种作用(促癌或抗癌)。在这项研究中，我们首次指出，在孟加拉国癌症高发区饮用水中浓度等于平均浓度的3微米砷，同时以不同的途径表达了其对人鳞状细胞癌HSC5细胞的双向作用。3µM砷通过上调HSC5细胞MT1-MMPs的表达和下调p14ARF的表达来促进细胞的侵袭，同时通过抑制N-钙粘蛋白的表达和上调p21(WAF1/CIP1)的转录和蛋白水平来诱导细胞的凋亡。我们还发现，NSC405020抑制MT1-MMPs的表达可减少砷对HSC5细胞的侵袭，其机制可能与细胞外信号调节蛋白激酶(PERK)的磷酸化有关。综上所述，我们的生物学和生化研究结果表明，砷作为致癌物和抗癌剂在人鳞状细胞癌HSC5细胞中具有双向作用，具有不同的作用途径。我们的结果可能为进一步研究寻找更好的治疗砷诱发癌症，特别是鳞状细胞癌的方法提供重要的科学证据。
Bidirectional cancer-promoting and anti-cancer effects of arsenic for cancer cells have been revealed in previous studies. However, each of these effects (cancer-promoting or anti-cancer) was found in different cells at different treated-concentration of arsenic. In this study, we for the first time indicated that arsenic at concentration of 3 µM, equal to average concentration in drinking water in cancer-prone areas in Bangladesh, simultaneously expressed its bidirectional effects on human squamous cell carcinoma HSC5 cells with distinct pathways. Treatment with 3 µM of arsenic promoted cell invasion via upregulation of expression of MT1-MMP and downregulation of expression of p14ARF and simultaneously induced cell apoptosis through inhibition of expression of N-cadherin and increase of expression of p21(WAF1/CIP1) at both transcript and protein levels in HSC5 cells. We also showed that inhibition of MT1-MMP expression by NSC405020 resulted in decrease of arsenic-mediated invasion of HSC5 cells involving decrease in phosphorylated extracellular signal-regulated kinases (pERK). Taken together, our biological and biochemical findings suggested that arsenic expressed bidirectional effects as a carcinogen and an anti-cancer agent in human squamous cell carcinoma HSC5 cells with distinct pathways. Our results might play an important scientific evident for further studies to find out a better way in treatment of arsenic-induced cancers, especially in squamous cell carcinoma.
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N-钙粘着蛋白在乳腺癌细胞中的外源表达会诱导细胞迁移，侵袭和转移。
影响因子：
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作者：
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