Slivova Veronika, Zaloga Gary, DeMichele Stephen J, Mukerji Pradip, Huang Yung-Sheng, Siddiqui Rafat, Harvey Kevin, Valachovicova Tatiana, Sliva Daniel
Cancer Research Laboratory, Methodist Research Institute, Indianapolis, IN 46202, USA.
Nutr Cancer. 2005;52(1):66-73. doi: 10.1207/s15327914nc5201_9.
Many epidemiological studies have suggested that consumption of green tea may decrease the risk of cancer. The chemopreventive effect of green tea polyphenols (GTP) has been demonstrated through the inhibition of cell proliferation and angiogenesis in cell culture and animal models of breast cancer. Metastasis of breast cancer is the major reason for the high mortality of breast cancer patients and is directly linked to the invasive behavior of breast cancer cells. Cancer metastasis consists of several interdependent processes including cancer cell adhesion, cancer cell migration, and invasion of cancer cells. In this study, we evaluated the effect of GTP on human breast cancer cells, and we show that in addition to inhibiting cell growth, GTP also suppressed the invasive behavior of MDA-MB-231 cells. These anti-invasive effects of GTP were the result of the inhibition of constitutively active transcription factors AP-1 and NF-kappaB, which further suppressed secretion of urokinase plasminogen activator (uPA) from breast cancer cells. Based on these results, it can be hypothesized that GTP treatment resulted in the inhibition of formation of signaling complexes responsible for cell adhesion and migration (uPA, uPA receptor, vitronectin, integrin receptor) and cell invasion (uPA, uPA receptor). Our results indicate that GTP may contribute to the anticancer effects of green tea by inhibiting the invasive behavior of cancer cells.
许多流行病学研究表明，饮用绿茶可能降低患癌风险。绿茶多酚（GTP）的化学预防作用已在乳腺癌细胞培养和动物模型中通过抑制细胞增殖和血管生成得到证实。乳腺癌转移是乳腺癌患者高死亡率的主要原因，并且与乳腺癌细胞的侵袭行为直接相关。癌症转移由几个相互依存的过程组成，包括癌细胞黏附、癌细胞迁移以及癌细胞侵袭。在本研究中，我们评估了GTP对人乳腺癌细胞的作用，并且我们发现，除了抑制细胞生长外，GTP还抑制了MDA-MB-231细胞的侵袭行为。GTP的这些抗侵袭作用是抑制组成型活性转录因子AP-1和核因子κB的结果，这进一步抑制了乳腺癌细胞中尿激酶型纤溶酶原激活剂（uPA）的分泌。基于这些结果，可以推测GTP处理导致负责细胞黏附和迁移（uPA、uPA受体、玻连蛋白、整合素受体）以及细胞侵袭（uPA、uPA受体）的信号复合物形成受到抑制。我们的结果表明，GTP可能通过抑制癌细胞的侵袭行为而有助于绿茶的抗癌作用。
