海参多糖抑制人肾癌细胞A498的生长转移作用机制

肾细胞癌(RCC)是最常见的恶性癌之一,癌症转移是目前导致肾癌患者死亡的主要原因之一。MMP-9被发现在许多具有侵袭性和转移能力的人类癌症中过表达,其表达和分泌受到NF-κB调控;VEGF在维持原发性癌和转移瘤生长所需的血管生成中发挥重要作用,其表达也受到活化的NF-κB调节。海参的多种活性物质在抗氧化、抗菌和抗癌方面都有出色的作用,而抗癌的主要机制则包括诱导癌细胞凋亡、抑制癌细胞生长、减少癌细胞转移等。本研究通过利用不同浓度的海参多糖处理人肾癌细胞A498,采用MTT细胞增殖实验、粘附实验、迁移实验和小室侵袭实验,研究了海参多糖对A498细胞的生长转移的影响;采用蛋白印记法检测了海参多糖对A498细胞内MMP-9、NF-κBp65和VEGF表达水平的影响。结果表明,海参多糖能够显著抑制A498细胞的增殖活力、粘附能力、迁移能力和侵袭能力,并且全都表现出明显的剂量依赖性;中浓度(100μg/mL)和高浓度(200μg/mL)的海参多糖能够显著下调A498细胞内MMP-9、NF-κBp65和VEGF的表达。这些结果说明海参多糖能有效抑制人肾癌细胞A498的生长、转移和侵袭,可能的机制是通过抑制NF-κB信号通路下调MMP-9和VEGF的表达,从而发挥抗癌细胞转移的作用。

Mechanism of the Effect of Sea Cucumber Polysaccharide on Inhibiting the Growth and Metastasis of Human RCC A498 Cells

Renal cell carcinoma(RCC) is one of the most common malignant cancers, and cancer metastasis is one of the leading causes of death in RCC patients. MMP-9 has been found to be overexpressed in many human cancers with invasive and metastatic potential, and its expression and secretion were regulated by NF-κB;VEGF plays an important role in maintaining angiogenesis required for primary cancer and metastatic tumor growth, its expression is also found to be regulated by activated NF-κB. Various active substances from sea cucumber have excellent effects on anti-oxidation, anti-bacterial and anti-cancer, and the main mechanisms of anti-cancer including induction of apoptosis of cancer cells, inhibition of cancer cell growth, and reduction of cancer cell metastasis.In this study, human RCC A498 cells were treated with different concentrations of sea cucumber polysaccharide,and the effects of sea cucumber polysaccharide on the growth and metastasis of A498 cells were studied by MTT cell proliferation assay, adhesion assay, migration assay and chamber invasion assay. The effects of sea cucumber polysaccharide on the expression of MMP-9, NF-κBp65 and VEGF in A498 cells were also detected. The results showed that sea cucumber polysaccharide could significantly inhibit the proliferation, adhesion, migration and invasion of A498 cells, and all showed significant dose-dependent;medium concentration(100 μg/mL) and high concentration(200 μg/mL) of Sea cucumber polysaccharide can significantly down-regulate the expression of MMP-9, NF-κBp65 and VEGF in A498 cells. These results indicated that sea cucumber polysaccharide could effectively inhibit the growth, metastasis and invasion of human RCC A498 cells. The mechanism may be to down-regulate the expression of MMP-9 and VEGF by inhibiting NF-κB signaling pathway, thereby exerting its anti-metastasis function.