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首页> 美国卫生研究院文献>Oncology Letters >α-Mangostin suppresses lipopolysaccharide-induced invasion by inhibiting matrix metalloproteinase-2/9 and increasing E-cadherin expression through extracellular signal-regulated kinase signaling in pancreatic cancer cells
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α-Mangostin suppresses lipopolysaccharide-induced invasion by inhibiting matrix metalloproteinase-2/9 and increasing E-cadherin expression through extracellular signal-regulated kinase signaling in pancreatic cancer cells

机译：α-Mangostin通过抑制基质金属蛋白酶-2/9并通过细胞外信号调节激酶信号通路增加胰腺癌细胞中的E-钙粘蛋白表达来抑制脂多糖诱导的侵袭

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摘要

Invasion and metastasis are major factors in the poor prognosis of pancreatic cancer, which remains one of the most aggressive and lethal diseases worldwide. α-mangostin, a major xanthone compound identified in the pericarp of mangosteen (Garcinia mangostana, Linn; GML), possesses unique biological activities, including antioxidant, antitumor and anti-inflammatory effects. Whether α-mangostin is able to inhibit the invasive ability of pancreatic cancer cells has not been elucidated. In the present study, α-mangostin was shown to inhibit the invasive ability of the pancreatic cancer cell lines MIAPaCa-2 and BxPC-3. The results showed that α-mangostin inhibited the growth of the pancreatic cancer cells in a dose- and time-dependent manner. At concentrations of <5 μM, α-mangostin had no significant effects on cytotoxicity, but significantly inhibited the invasion and migration of pancreatic cancer cells and the expression of matrix metalloproteinase (MMP)-2 and MMP-9, while increasing the expression of E-cadherin. The present data also showed that α-mangostin exerted an inhibitory effect on the phosphorylation of extracellular-signal-regulated kinase (ERK). Furthermore, the reduction of ERK phosphorylation by small interfering RNA (siRNA) potentiated the effect of α-mangostin. Taken together, the data suggest that α-mangostin inhibited the invasion and metastasis of pancreatic cancer cells by reducing MMP-2 and MMP-9 expression, increasing E-cadherin expression and suppressing the ERK signaling pathway. The present study suggests that α-mangostin may be a promising agent against pancreatic cancer.
机译：侵袭和转移是胰腺癌预后不良的主要因素，胰腺癌仍然是全世界最具侵略性和致死性的疾病之一。 α-mangostin是在山竹果皮（Garcinia mangostana，Linn; GML）的果皮中鉴定出的一种主要的蒽酮化合物，具有独特的生物学活性，包括抗氧化，抗肿瘤和抗炎作用。尚不清楚α-芒果素是否能够抑制胰腺癌细胞的侵袭能力。在本研究中，α-芒果素显示出抑制胰腺癌细胞系MIAPaCa-2和BxPC-3的侵袭能力。结果表明，α-芒果素以剂量和时间依赖性方式抑制胰腺癌细胞的生长。在<5μM的浓度下，α-Mangostin对细胞毒性无明显影响，但显着抑制胰腺癌细胞的侵袭和迁移以及基质金属蛋白酶（MMP）-2和MMP-9的表达，同时增加E的表达-钙黏着蛋白。本数据还表明，α-Mangostin对细胞外信号调节激酶（ERK）的磷酸化具有抑制作用。此外，小干扰RNA（siRNA）减少了ERK磷酸化，增强了α-芒果的作用。两者合计，数据表明α-Mangostin通过降低MMP-2和MMP-9表达，增加E-钙黏着蛋白表达并抑制ERK信号通路来抑制胰腺癌细胞的侵袭和转移。本研究表明，α-芒果素可能是抗胰腺癌的有前途的药物。

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