Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA.
Anticancer Res. 2012 Jul;32(7):2647-55.
Non-small cell lung cancer (NSCLC), accounting for 80% of lung cancers, is the leading cause of all cancer deaths. Previously, we demonstrated that delta-tocotrienol inhibits NSCLC cell proliferation, invasion and induces apoptosis by down-regulation of the Notch-1 signaling pathway. The objective of this study was to investigate whether delta-tocotrienol, could enhance the anticancer effects of cisplatin. Treatment with a combination of delta-tocotrienol and cisplatin resulted in a dose-dependent, significant inhibition of cell growth, migration, invasiveness, and induction of apoptosis in NSCLC cells, as compared to the single agents. This was associated with a decrease in NF-κB DNA binding activity, decrease in Notch-1, Hes-1, Bcl-2 and increase in cleaved Caspase-3 and PARP expressions. These results suggest that down-regulation of Notch-1, via inhibition of NF-κB signaling pathways by delta-tocotrienol and cisplatin, in combination, could provide a potential novel approach for tumor arrest in NSCLC, while lowering the effective dose of cisplatin.
非小细胞肺癌（NSCLC）占肺癌的 80%，是所有癌症死亡的主要原因。此前，我们已经证明，δ-生育三烯酚通过下调 Notch-1 信号通路抑制 NSCLC 细胞增殖、侵袭并诱导细胞凋亡。本研究旨在探讨 δ-生育三烯酚是否可以增强顺铂的抗癌作用。与单一药物相比，δ-生育三烯酚和顺铂联合治疗可导致 NSCLC 细胞的生长、迁移、侵袭和凋亡呈剂量依赖性显著抑制。这与 NF-κB DNA 结合活性降低、Notch-1、Hes-1、Bcl-2 减少以及 cleaved Caspase-3 和 PARP 表达增加有关。这些结果表明，通过抑制 NF-κB 信号通路，δ-生育三烯酚和顺铂联合下调 Notch-1，可能为 NSCLC 的肿瘤抑制提供一种新的潜在方法，同时降低顺铂的有效剂量。
