Department of Oncology, Huaiyin Hospital of Huai'an City, Huai'an, China.
Department of Respiration, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
Int J Nanomedicine. 2017 Oct 17;12:7627-7651. doi: 10.2147/IJN.S127549. eCollection 2017.
Actein (AT) is a triterpene glycoside isolated from the rhizomes of that has been investigated for its antitumor effects. AT treatment leads to apoptosis in various cell types, including breast cancer cells, by regulating different signaling pathways. Iron oxide (FeO) magnetic nanoparticles (MNPs) are nanomaterials with biocompatible activity and low toxicity. In the present study, the possible benefits of AT in combination with MNPs on non-small-cell lung cancer (NSCLC) were explored in in vitro and in vivo studies. AT-MNP treatment contributed to apoptosis in NSCLC cells, as evidenced by activation of the caspase 3-signaling pathway, which was accompanied by downregulation of the antiapoptotic proteins Bcl2 and BclXL, and upregulation of the proapoptotic signals Bax and Bad. The death receptors of TRAIL were also elevated following AT-MNP treatment in a p53-dependent manner. Furthermore, a mouse xenograft model in vivo revealed that AT-MNP treatment exhibited no toxicity and suppressed NSCLC growth compared to either AT or MNP monotherapies. In conclusion, this study suggests a novel therapy to induce apoptosis in suppressing NSCLC growth in a p53-dependent manner by combining AT with FeO MNPs.
白头翁（AT）是从白头翁根茎中分离得到的一种三萜糖苷，已被研究用于其抗肿瘤作用。AT 通过调节不同的信号通路，导致包括乳腺癌细胞在内的各种细胞类型发生凋亡。氧化铁（FeO）磁性纳米粒子（MNPs）是一种具有生物相容性和低毒性的纳米材料。在本研究中，通过体外和体内研究探索了 AT 与 MNPs 联合应用于非小细胞肺癌（NSCLC）的可能益处。AT-MNP 治疗促进了 NSCLC 细胞的凋亡，这一点可通过 caspase 3 信号通路的激活得到证明，该通路伴随着抗凋亡蛋白 Bcl2 和 BclXL 的下调，以及促凋亡信号 Bax 和 Bad 的上调。TRAIL 的死亡受体也在 p53 依赖性方式下，在 AT-MNP 治疗后升高。此外，体内小鼠异种移植模型表明，与 AT 或 MNP 单药治疗相比，AT-MNP 治疗没有毒性，并抑制了 NSCLC 的生长。综上所述，本研究提出了一种新的治疗方法，通过将 AT 与 FeO MNPs 联合应用，以 p53 依赖性方式诱导凋亡，从而抑制 NSCLC 的生长。
