Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells.
Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells.
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DOI：
10.2147/bctt.s124860
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Hyder SM
中科院分区：
文献类型：
--
作者：
Cook MT;Liang Y;Besch-Williford C;Hyder SM
大多数三阴性乳腺癌(TNBC)的乳腺癌相关死亡发生在癌细胞转移和继发部位肿瘤发展之后。由于TNBCs缺乏当前化疗方案所靶向的三种受体，它们通常采用极具侵略性和高毒性的非靶向治疗策略。患有TNBC的妇女经常发生源自耐药残留细胞的转移灶，并且预后不良。出于这个原因，人们寻求更安全和更有效的新的治疗策略。木犀草素(LU)是一种天然存在的无毒植物化合物，已被证明对几种类型的癌症有效。考虑到这一点，我们进行了体内和体外研究，以确定LU是否可以抑制TNBC的转移。在小鼠体内转移模型中，LU抑制人MDA-MB-435和MDA-MB-231(4175)LM2 TNBC细胞向肺部的转移。在体外实验中，LU抑制了MDA-MB-435和MDA-MB-231(4175)LM2细胞的迁移和存活。此外，LU还可诱导MDA-MB-231(4175)LM2细胞发生凋亡。相对较低水平(10µM)的LU显著抑制了MDA-MB-231(4175)LM2细胞血管内皮生长因子(VEGF)的分泌，表明其具有抑制强大的血管生成和细胞生存因子的能力。此外，在暴露于抗血管内皮生长因子受体KDR的抗体时，MDA-MB-231(4175)LM2细胞的迁移受到抑制，但不受暴露于VEGF165抗体的抑制。综上所述，这些数据表明，LU的抗转移特性可能部分是由于它能够阻断VEGF的产生和KDR介导的活性，从而抑制肿瘤细胞的迁移。这些研究表明，LU作为治疗TNBC的潜在选择值得进一步研究。
Most breast cancer-related deaths from triple-negative breast cancer (TNBC) occur following metastasis of cancer cells and development of tumors at secondary sites. Because TNBCs lack the three receptors targeted by current chemotherapeutic regimens, they are typically treated with extremely aggressive and highly toxic non-targeted treatment strategies. Women with TNBC frequently develop metastatic lesions originating from drug-resistant residual cells and have poor prognosis. For this reason, novel therapeutic strategies that are safer and more effective are sought. Luteolin (LU) is a naturally occurring, non-toxic plant compound that has proven effective against several types of cancer. With this in mind, we conducted in vivo and in vitro studies to determine whether LU might suppress metastasis of TNBC. In an in vivo mouse metastasis model, LU suppressed metastasis of human MDA-MB-435 and MDA-MB-231 (4175) LM2 TNBC cells to the lungs. In in vitro assays, LU inhibited cell migration and viability of MDA-MB-435 and MDA-MB-231 (4175) LM2 cells. Further, LU induced apoptosis in MDA-MB-231 (4175) LM2 cells. Relatively low levels (10 µM) of LU significantly inhibited vascular endothelial growth factor (VEGF) secretion in MDA-MB-231 (4175) LM2 cells, suggesting that it has the ability to suppress a potent angiogenic and cell survival factor. In addition, migration of MDA-MB-231 (4175) LM2 cells was inhibited upon exposure to an antibody against the VEGF receptor, KDR, but not by exposure to a VEGF165 antibody. Collectively, these data suggest that the anti-metastatic properties of LU may, in part, be due to its ability to block VEGF production and KDR-mediated activity, thereby inhibiting tumor cell migration. These studies suggest that LU deserves further investigation as a potential treatment option for women with TNBC.