Inhibition of B16F-10 Melanoma-Induced Lung Metastasis in C57BL/6 Mice by Aerva lanata via Induction of Apoptosis
Inhibition of B16F-10 Melanoma-Induced Lung Metastasis in C57BL/6 Mice by Aerva lanata via Induction of Apoptosis
复制标题
DOI：
10.1177/1534735412443853
复制
发表时间：
2013-01-01
影响因子：
2.9
通讯作者：
Kuttan, Girija
中科院分区：
文献类型：
--
作者：
Siveen, Kodappully Sivaraman;Kuttan, Girija
在这项研究中，使用B16 F-10黑色素瘤诱导的肺转移模型评估了绵状Aerva lanata的乙醇提取物的抗转移潜力。通过侧尾静脉注射高转移性B16 F-10黑色素瘤细胞在C57 BL/6小鼠中诱导转移。同时用羊毛状放线菌处理抑制了肺中肿瘤结节的形成（70.53%），并且转移性荷瘤动物的存活率增加了65.3%。这些结果与生化参数，如肺胶原羟脯氨酸，氨基己糖，和糖醛酸含量;血清唾液酸和γ-谷氨酰转肽酶水平;和组织病理学分析。在体外研究中，使用B16 F-10细胞表明，羊毛状放线菌抑制肿瘤细胞的迁移，细胞通过I型胶原蛋白涂层的聚碳酸酯过滤器和激活的基质金属蛋白酶的侵袭。用羊毛状放线菌处理诱导凋亡反应，其特征在于凋亡形态、典型的DNA片段化梯形和通过TUNEL测定检测DNA中的3'羟基末端。亚G 0/G1期细胞百分比增加，表明细胞周期停滞。羊毛脂处理导致B16 F-10细胞中bcl-2和cyclin-D1表达下调，p53、bax、caspase-9、caspase-3、p21和p27基因表达上调。促炎细胞因子的产生和基因表达也被发现在羊毛脂处理的细胞下调。
In this study, the antimetastatic potential of the ethanolic extract of Aerva lanata was evaluated using the B16F-10 melanoma-induced lung metastasis model. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Simultaneous treatment with A lanata inhibited tumor nodule formation in the lungs (70.53%), and there was a 65.3% increase in the survival rate of metastatic tumor-bearing animals. These results correlated with biochemical parameters such as lung collagen hydroxyproline, hexosamine, and uronic acid contents; serum sialic acid and gamma-glutamyl transpeptidase levels; and histopathological analysis. In vitro studies using B16F-10 cells showed that A lanata inhibited migration of tumor cells, cell invasion through type-I collagen-coated polycarbonate filter and activation of matrix metalloproteinases. Treatment with A lanata induced apoptotic response, characterized by apoptotic morphology, a typical ladder of DNA fragmentation, and detection of 3' hydroxyl ends in DNA by TUNEL assay. There was an increase in the percentage of cells in the sub-G0/G1 phase indicating cell cycle arrest. A lanata treatment resulted in downregulation of bcl-2 and cyclin-D1 expression and upregulation of p53, bax, caspase-9, caspase-3, p21, and p27 gene expression in B16F-10 cells. Proinflammatory cytokine production and gene expression were also found to be downregulated in A lanata-treated cells.