Erianin Inhibited IDO-induced Angiogenesis In Lewis Lung Cancer Cells

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. Erianin is a natural product isolated from Dendrobium chrysotoxum Lindl. Previous studies have demonstrated the antitumor activity of erianin in many kinds of cancers. And IDO dysregulation in cancer pathogenesis has been valued. Current researches of IDO mainly focus on cancer-related immunosuppression, but IDO also has non-immune functions including regulating tumor angiogenesis. So this study aims to link erianin with IDO, and attempts to dicuss whether erianin can regulate expression of IDO to play its role in anti-angiogenesis. This can provide theory basis for the anti-angiogenesis therapy of lung cancer.Here we first investigated the influence of biological behaviors of IDO on Lewis lung cancer cells. 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. Then, Western blot, Real-time PCR and HPLC assays demonstrated that erianin suppressed expression and enzyme ability of IDO. Next, tranwell assay revealed that erianin inhibited IDO-induced metastasis and invasion ability of 2LL cells significantly. And erianin not only blocked IDO-induced tube formation of HUVECs, but also suppressed VM formation of 2LL-IDO cells. Finally, we examined the expression of key signal molecules involved in the process of angiogenesis which was regulated by erianin. 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. So our study will be more effective to lay a basis on cutting off the blood supply for tumor, which is beneficial to prevent and treat the malignant tumors.