Minhang Hospital, Fudan University, China.
School of Pharmacy, East China University of Science and Technology, China.
Biomed Pharmacother. 2017 Apr;88:521-528. doi: 10.1016/j.biopha.2017.01.090. Epub 2017 Jan 24.
Tumor angiogenesis is the key process in tumor growth and metastasis, and transfers essential nutrients for solid tumor. Inhibition of tumor angiogenesis has been recognized as a more effective anti-cancer strategy for NSCLC and has acquired certain therapeutic effects. IDO has non-immune functions including regulating tumor angiogenesis and IDO dysregulation in cancer pathogenesis has been valued. Erianin is a natural product isolated from Dendrobium chrysotoxum Lindl. The antitumor activity of erianin in many kinds of cancers had been demonstrated in previous studies. In this study, we demonstrated that IDO could promote the attachment of 2LL cells, the ability of migration, invasion and VM formation, as well as the tubules forming ability of HUVECs. We also find that erianin suppressed expression and enzyme ability of IDO and erianin could inhibit IDO-induced metastasis and invasion ability of 2LL cells significantly. Erianin not only blocked IDO-induced tube formation of HUVECs, but also suppressed VM formation of 2LL-IDO cells. What's more, we examined that Erianin might play its role in angiogenesis through down-regulating phosphorylation of JAK2/STAT3, inhibiting its downstream target genes MMP-2/-9 and some inflammatory mediators (COX-2, HIF-1α and IL-6), which were all induced by IDO. All these results indicated that erianin had anti-angiogenesis ability and could inhibit the expresison of IDO to prevent and treat the malignant tumors.
肿瘤血管生成是肿瘤生长和转移的关键过程,为实体瘤提供了必需的营养物质。抑制肿瘤血管生成已被认为是治疗 NSCLC 的一种更有效的抗癌策略,并取得了一定的治疗效果。IDO 具有非免疫功能,包括调节肿瘤血管生成,癌症发病机制中的 IDO 失调已受到重视。钩吻素子是从吊石苣苔中分离得到的一种天然产物。在以前的研究中已经证明了钩吻素子在多种癌症中的抗肿瘤活性。在这项研究中,我们证明了 IDO 可以促进 2LL 细胞的附着、迁移、侵袭和 VM 形成能力,以及 HUVECs 的管腔形成能力。我们还发现,钩吻素子抑制了 IDO 的表达和酶活性,并且钩吻素子可以显著抑制 IDO 诱导的 2LL 细胞的转移和侵袭能力。钩吻素子不仅阻断了 IDO 诱导的 HUVEC 管腔形成,还抑制了 2LL-IDO 细胞的 VM 形成。此外,我们研究发现,钩吻素子可能通过下调 JAK2/STAT3 的磷酸化,抑制其下游靶基因 MMP-2/-9 和一些炎症介质(COX-2、HIF-1α 和 IL-6)来发挥其在血管生成中的作用,这些基因均由 IDO 诱导。这些结果表明,钩吻素子具有抗血管生成能力,并能抑制 IDO 的表达,从而预防和治疗恶性肿瘤。