Benzopyrene promotes lung cancer A549 cell migration and invasion through up-regulating cytokine IL8 and chemokines CCL2 and CCL3 expression
Benzopyrene promotes lung cancer A549 cell migration and invasion through up-regulating cytokine IL8 and chemokines CCL2 and CCL3 expression
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苯并芘通过上调细胞因子IL8和趋化因子CCL2和CCL3表达促进肺癌A549细胞迁移和侵袭
DOI：
10.1177/1535370216644530
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发表时间：
2016-04
影响因子：
3.2
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Zhang J;Chang L;Jin H;Xia Y;Wang L;He W;Li W;Chen H
烟草源致癌物苯并芘（B[a]P）在肺癌转移中的作用尚未见报道。本研究以肺癌A549细胞为研究对象，探讨烟草源B[a]P对肺癌细胞侵袭转移的影响及其机制。分别采用MTT法、Transwell法和划痕法检测烟草致癌物对A549细胞增殖、转移和侵袭的影响。采用酶联免疫吸附试验检测烟草致癌物对细胞因子和趋化因子分泌的影响。此外，使用siRNA介导的基因沉默评估炎症因子表达与癌细胞迁移和侵袭之间的相关性。结果表明，随着作用时间的延长，B[a]P和4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮在高、低剂量下对A549细胞增殖的影响均无显著性差异。与对照组相比，4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮对A549细胞的迁移和侵袭能力无显著性差异，而B[a]P可显著增加A549细胞的迁移和侵袭能力（P < 0.05）。因此，除IL-6、IL-8、CCL-2和CCL-3外，B[a]P处理组的分泌物与对照组相比显著增加（P < 0.05）。当CCL-2和CCL-3沉默后，A549细胞的迁移和侵袭能力分别显著低于对照组（P < 0.05），而IL-8沉默后，A549细胞的迁移和侵袭能力显著低于对照组（P < 0.01）。综上所述，本研究表明吸烟与肺癌转移可能存在显著相关性。B[a]P可能通过上调IL-8、CCL-2和CCL-3的表达而促进肺癌转移。
Tobacco-sourced carcinogen including benzopyrene (B[a]P) in lung cancer metastasis has not been fully reported. In this study, lung carcinoma A549 cell line was used to investigate the potential roles of tobacco-sourced B[a]P on cell metastasis and invasion and to assess its underlying mechanism. Effects of tobacco-sourced carcinogen on A549 cell proliferation, metastasis, and invasion were analyzed using MTT assay, Transwell assay, and scratch method, respectively. The effects of tobacco-sourced carcinogen on cytokines and chemokines secretion were detected using enzyme-linked immunosorbent assay. Moreover, correlation between inflammatory factor expression and cancer cell migration and invasion was assessed using siRNA-mediated gene silencing. Data showed that both B[a]P and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone either at high or low dose performed no significant difference on A549 cell proliferation with time increasing. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone performed no significant difference on A549 cell migration and invasion while B[a]P significantly increased A549 cell migration and invasion compared to the control group (P < 0.05). Consequently, except for IL-6, IL-8, CCL-2, and CCL-3, secretions were significantly increased by B[a]P treatment compared to the control (P < 0.05). Furthermore, when CCL-2 and CCL-3 were silenced, the migrated and invasive A549 cells were significantly decreased compared to the control, respectively (P < 0.05), while silenced IL-8 drastically decreased the migrated and invasive cells compared to the control (P < 0.01). Taken together, this study illustrated that there may be significant correlation between smoking and lung cancer metastasis. B[a]P maybe an excellent contributor for lung cancer metastasis through up-regulating IL-8, CCL-2, and CCL-3 expression.
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