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Evodiamine inhibits the migration and invasion of nasopharyngeal carcinoma cells in vitro via repressing MMP-2 expression

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Abstract

Purpose

Evodiamine is one of active alkaloids isolated from the traditional Chinese medicine Evodia rutaecarpa Bentham and has various pharmacological properties. In this study, we investigated its effects on the migration, invasion, and associated mechanism in human nasopharyngeal carcinoma (NPC) cells.

Methods

Cell viability was determined by MTT assay after evodiamine treatment. Wound-healing assay and Boyden transwell system were used to evaluate the inhibitory effects of evodiamine on cell migration and invasion. MMP-2/9 activity was determined using commercial detection kits. The levels of associated proteins involved in the regulation of cell migration and invasion were analyzed by Western blotting.

Results

Evodiamine effectively inhibited the migration and invasion of HONE1 and CNE1 cells, and hardly affected cell proliferation, but significantly suppressed cell adhesion activity in vitro. Additionally, evodiamine treatment significantly decreased mRNA and protein levels of MMP-2 and its activity in the NPC cells, but had little effects on MMP-9 mRNA and protein levels and its activity. Further investigation revealed that evodiamine inhibited the translocation of NF-κB p65, which involves the regulation of MMP-2 expression in cancer invasion. Additionally, evodiamine treatment did not significantly affect the protein levels of JNK, p38, Akt, and their phosphorylated forms and ERK1/2, but strongly attenuated ERK1/2 phosphorylation level, which at least partly accounts for the signal pathway of evodiamine-inhibited migration and invasion of NPC cells.

Conclusion

These findings demonstrate that evodiamine inhibits the migration and invasiveness of NPC cells, and it is probably a potential agent for the treatment of NPC invasion and metastasis.

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Abbreviations

MMP:

Matrix metalloproteinase

MMP-2:

Matrix metalloproteinase-2

MMP-9:

Matrix metalloproteinase-9

NPC:

Nasopharyngeal carcinoma

JNK:

c-Jun N-terminal kinase

ERK1/2:

Extracellular signal-regulated kinase 1/2

ECM:

Extracellular matrix

MTT:

3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

RT-PCR:

Reverse transcription polymerase chain reaction

MAPKs:

Mitogen-activated protein kinases

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Acknowledgments

We thank Dr. Shelly Crooks for the critical reading and English proof reading of this manuscript.

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    Authors and Affiliations

    1. Otorhinolaryngologieal Department, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei Province, China

      Xianbing Peng, Qun Zhang, Jin Li, Lixin Wang & Ping Ai

    2. Otorhinolaryngologieal Department, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, China

      Yi Zeng

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    1. Xianbing Peng
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    Correspondence to Qun Zhang.

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    Xianbing Peng and Qun Zhang have contributed equally to this work.

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    Peng, X., Zhang, Q., Zeng, Y. et al. Evodiamine inhibits the migration and invasion of nasopharyngeal carcinoma cells in vitro via repressing MMP-2 expression. Cancer Chemother Pharmacol 76, 1173–1184 (2015). https://doi.org/10.1007/s00280-015-2902-9

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