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Erianin inhibits indoleamine 2, 3-dioxygenase -induced tumor angiogenesis
Chang Su1, Peng Zhang2, Jianwen Liu2
1Minhang Hospital, Fudan University, China.
Abstract:
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.
Insights
Erianin, a natural compound, inhibits tumor angiogenesis by suppressing indoleamine 2,3-dioxygenase (IDO). This natural product blocks cancer cell invasion and blood vessel formation, offering potential for treating malignant tumors.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Tumor angiogenesis is crucial for tumor growth and metastasis.
- Inhibiting tumor angiogenesis is a key anti-cancer strategy, particularly for non-small cell lung cancer (NSCLC).
- Indoleamine 2,3-dioxygenase (IDO) plays a role in regulating tumor angiogenesis and its dysregulation is implicated in cancer.
Purpose of the Study:
- To investigate the effect of erianin on tumor angiogenesis.
- To explore the role of IDO in cancer cell metastasis and angiogenesis.
- To elucidate the molecular mechanisms by which erianin inhibits IDO-induced angiogenesis and metastasis.
Main Methods:
- Assessing the effects of IDO on 2LL cancer cell attachment, migration, invasion, and vascular mimicry (VM) formation.
- Evaluating the impact of erianin on IDO expression and enzymatic activity.
- Analyzing erianin's effects on IDO-induced HUVEC tube formation and 2LL cell VM formation.
- Investigating the molecular pathways involved, including JAK2/STAT3 phosphorylation and downstream targets like MMP-2/-9, COX-2, HIF-1α, and IL-6.
Main Results:
- IDO promotes 2LL cell attachment, migration, invasion, VM formation, and HUVEC tube formation.
- Erianin suppresses IDO expression and enzymatic activity.
- Erianin significantly inhibits IDO-induced metastasis, invasion, VM formation, and HUVEC tube formation.
- Erianin down-regulates JAK2/STAT3 phosphorylation and its downstream targets induced by IDO.
Conclusions:
- Erianin exhibits anti-angiogenesis properties.
- Erianin inhibits tumor progression by suppressing IDO expression and its associated pro-angiogenic and pro-metastatic effects.
- Erianin holds potential as a therapeutic agent for preventing and treating malignant tumors.
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