Bromoenol Lactone Attenuates Nicotine-Induced Breast Cancer Cell Proliferation and Migration.
Bromoenol Lactone Attenuates Nicotine-Induced Breast Cancer Cell Proliferation and Migration.
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DOI：
10.1371/journal.pone.0143277
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ndinguri M
中科院分区：
文献类型：
--
作者：
Calderon LE;Liu S;Arnold N;Breakall B;Rollins J;Ndinguri M
钙非依赖性组VIA磷脂酶A2（iPLA 2 β）和基质金属蛋白酶-9（MMP-9）在许多疾病状态中上调;它们与癌细胞迁移的关系是最近的研究主题。此外，介导尼古丁诱导的乳腺癌细胞进展的分子机制尚未得到充分研究。本研究旨在通过体外和体内技术研究iPLA 2 β是否介导尼古丁诱导的乳腺癌细胞增殖和迁移。随后，检查溴烯醇内酯（BEL）减轻尼古丁诱导的乳腺癌的严重性的能力。我们发现，BEL显着衰减基础和尼古丁诱导的4 T1乳腺癌细胞增殖，通过MTT增殖试验。通过划痕和transwell试验检测乳腺癌细胞迁移，其中发现BEL显著降低基础和尼古丁诱导的迁移。此外，发现尼古丁诱导的MMP-9表达以iPLA 2 β依赖性方式介导。这些结果表明，iPLA 2 β在介导基础和尼古丁诱导的乳腺癌细胞增殖和迁移中起关键作用。在体内小鼠乳腺癌模型中，发现BEL治疗显著降低基础（p<0.05）和尼古丁诱导的肿瘤生长（p<0.01）。免疫组化分析显示BEL降低尼古丁诱导的MMP-9、HIF-1 α和CD 31肿瘤组织表达。随后，观察到BEL减少尼古丁诱导的肺转移。目前的研究表明，尼古丁诱导的迁移是由MMP-9的产生以iPLA 2 β依赖性方式介导的。我们的数据表明，BEL是一种可能的化疗药物，因为它被发现可以减少尼古丁诱导的乳腺癌肿瘤生长和肺转移。
Calcium independent group VIA phospholipase A2 (iPLA2β) and Matrix Metalloproteinase-9 (MMP-9) are upregulated in many disease states; their involvement with cancer cell migration has been a recent subject for study. Further, the molecular mechanisms mediating nicotine-induced breast cancer cell progression have not been fully investigated. This study aims to investigate whether iPLA2β mediates nicotine-induced breast cancer cell proliferation and migration through both in-vitro and in-vivo techniques. Subsequently, the ability of Bromoenol Lactone (BEL) to attenuate the severity of nicotine-induced breast cancer was examined. We found that BEL significantly attenuated both basal and nicotine-induced 4T1 breast cancer cell proliferation, via an MTT proliferation assay. Breast cancer cell migration was examined by both a scratch and transwell assay, in which, BEL was found to significantly decrease both basal and nicotine-induced migration. Additionally, nicotine-induced MMP-9 expression was found to be mediated in an iPLA2β dependent manner. These results suggest that iPLA2β plays a critical role in mediating both basal and nicotine-induced breast cancer cell proliferation and migration in-vitro. In an in-vivo mouse breast cancer model, BEL treatment was found to significantly reduce both basal (p<0.05) and nicotine-induced tumor growth (p<0.01). Immunohistochemical analysis showed BEL decreased nicotine-induced MMP-9, HIF-1alpha, and CD31 tumor tissue expression. Subsequently, BEL was observed to reduce nicotine-induced lung metastasis. The present study indicates that nicotine-induced migration is mediated by MMP-9 production in an iPLA2β dependent manner. Our data suggests that BEL is a possible chemotherapeutic agent as it was found to reduce both nicotine-induced breast cancer tumor growth and lung metastasis.