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Growth inhibitor of human hepatic carcinoma HepG2 cells by evodiamine is associated with downregulation of PRAME

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Abstract

Hepatocellular carcinoma (HCC) patients have low 5-year survival due to the delayed diagnosis, so it is necessary to develop an alternative treatment. Preferentially expressed antigen of melanoma (PRAME) has a high expression in HCC patients, and the effects of evodiamine on HCC are less characterized, although evodiamine has anti-tumor activities in several tumor types. To investigate the effects of evodiamine on PRAME expression, the in vitro PRAME expression in HepG2 cells after incubated with evodiamine was determined by RT-PCR and western blot. Cell viability, migration, invasion, and apoptosis of evodiamine-incubated HepG2 cells were evaluated by Cell Counting Kit-8, wound healing, transwell assay, and Annexin V-FITC/PI double-staining assay, respectively. To evaluate the mechanism of the regulation of evodiamine on the PRAME expression, chromatin immunoprecipitation coupled with quantitative PCR was employed. Xenograft model was used to evaluate the effects of evodiamine on tumor growth, survival rate, and the PRAME expression. The PRAME expression was inhibited in evodiamine-treated HepG2 cells in vitro and in vivo. The tumor metastasis and growth were inhibited resulting from evodiamine incubation. The evodiamine inhibited the PRAME expression through trimethylation of H3K27. In this study, evodiamine contributes to in vitro and in vivo tumor cell growth inhibition. To achieve this inhibition, the PRAME expression may be repressed through trimethylation resulting from epigenetic regulation of evodiamine.

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Author contribution statement

Hanzhang Zhu conceived and designed the research. Ke Ge and Jun Lu analyzed the data. Changku Jia wrote the manuscript. All authors read and approved the manuscript.

Funding

The study was supported by the Zhejiang Traditional Chinese Medicine Science and Technology Plan Project (2018ZA081).

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Authors and Affiliations

  1. Department of Hepatopancreatobiliary Surgery, Hangzhou First People’s Hospital, The Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, 310006, Zhejiang, China

    Hanzhang Zhu, Ke Ge, Jun Lu & Changku Jia

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  1. Hanzhang Zhu
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  2. Ke Ge
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  3. Jun Lu
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  4. Changku Jia
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Correspondence to Changku Jia.

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All procedures were approved by the Institutional Research Ethics Committee of Hangzhou First People’s Hospital.

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Zhu, H., Ge, K., Lu, J. et al. Growth inhibitor of human hepatic carcinoma HepG2 cells by evodiamine is associated with downregulation of PRAME. Naunyn-Schmiedeberg's Arch Pharmacol 392, 1551–1560 (2019). https://doi.org/10.1007/s00210-019-01701-7

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  • DOI: https://doi.org/10.1007/s00210-019-01701-7

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