Cancer Research Unit, Research Division 151, VA Medical Center, 4801 Linwood Blvd, Kansas City, MO, 64128, USA.
J Cell Commun Signal. 2011 Dec;5(4):317-24. doi: 10.1007/s12079-011-0138-y. Epub 2011 Jun 27.
It is estimated that one in eight women will be affected with cancer during their lives, which means over 1 million women worldwide will be diagnosed with breast cancer in the year of 2011. Roughly, 70% of breast cancer will be estrogen receptor-alpha (ER-α) positive. The presence of ER-α is associated with better prognosis and is able to determine if tumors will respond to the estrogen-blocking/ER-antagonist drug Tamoxifen (TAM). However, a significant fraction of ER-positive tumors respond with minimal or no response to TAM. It is unclear why some breast cancer cells resist TAM and how to make these cells respond. Early evidence suggests Pomegranate fruit extracts (PFEs) exhibit an anticancer effect against some cancers. The objective of the study was to determine whether PFEs may able to enhance/sensitize the TAM's effect in ER-positive MCF-7 breast cancer cells. To test the hypothesis, we determined the effect of PFEs on sensitive and TAM-resistant-MCF-7 cell viability and cell death in the presence or absence of TAM under estrogenic or non-estrogenic culture environment. The present studies demonstrated that PFEs enhance the TAM action in both sensitive and TAM-resistant MCF-7 cells through the inhibition of cell viability (regular or estrogen-induced) by inducing cell-death machinery. Collectively, the results showed for the first time that pomegranate combined with TAM may represent a novel and a powerful approach to enhance and sensitize TAM action.
据估计，每 8 名女性中就有 1 人在其一生中会受到癌症的影响，这意味着全球每年将有超过 100 万名女性被诊断患有乳腺癌。大约 70%的乳腺癌为雌激素受体-α（ER-α）阳性。ER-α 的存在与更好的预后相关，并能够确定肿瘤是否对雌激素阻断/ER 拮抗剂药物他莫昔芬（TAM）有反应。然而，相当一部分 ER 阳性肿瘤对 TAM 的反应很小或没有反应。目前尚不清楚为什么一些乳腺癌细胞对 TAM 有抵抗力，以及如何使这些细胞有反应。早期证据表明，石榴果实提取物（PFEs）对某些癌症具有抗癌作用。本研究的目的是确定 PFEs 是否能够增强/敏化 TAM 在 ER 阳性 MCF-7 乳腺癌细胞中的作用。为了验证这一假设，我们在雌激素或非雌激素培养环境下，在存在或不存在 TAM 的情况下，确定了 PFEs 对敏感和 TAM 耐药 MCF-7 细胞活力和细胞死亡的影响。本研究表明，PFEs 通过诱导细胞死亡机制，抑制细胞活力（常规或雌激素诱导），从而增强 TAM 在敏感和 TAM 耐药 MCF-7 细胞中的作用。总的来说，这些结果首次表明，石榴与 TAM 联合使用可能代表一种增强和敏化 TAM 作用的新方法。
