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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
β-Elemene Inhibits Adrenocortical Carcinoma Cell Proliferation and Migration, and Induces Apoptosis by Up-Regulating
Yan Lin1,2,3,4, Tailin Guo1,2,3,4, Lishuang Che5
1Provincial Clinical College of Fujian Medical University, Fuzhou, China.
Abstract:
β-elemene has a variety of anti-inflammatory, antioxidant, and antitumor effects. Currently, the influence of β-elemene on adrenocortical carcinoma (ACC) malignant progression and action mechanism remains unclear. This research aims to explore the influence and action mechanism of β-elemene on ACC progression. The impacts of β-elemene on ACC cell viability, proliferation, migration, and apoptosis were investigated through CCK-8 assay, clone formation assay, Transwell experiment, Wound healing assay, and flow cytometry. The miR-486-3p expression was analyzed utilizing RT-qPCR. According to different databases, neuronal pentraxin 1 (NPTX1) is the predicted downstream target gene of miR-486-3p. Western blot and RT-qPCR were utilized to examine NPTX1 expression. Silencing miR-486-3p or Overexpression NPTX1 in ACC cells further explored whether β-elemene affects ACC cells by regulating miR-486-3p/NPTX1. Finally, a subcutaneous graft tumor model was constructed to investigate how β-elemene may impact tumor growth in vivo. β-elemene decreased the cell viability, hindered cell proliferation and migration capacity, and induced apoptosis of ACC cells. miR-486-3p level in ACC cells was notably reduced in comparison to normal cells, but treatment with β-elemene markedly increased miR-486-3p expression. Additionally, ACC cells showed high level of NPTX1, while miR-486-3p targeted negative regulation of NPTX1. Overexpression miR-486-3p hindered the malignant progression of ACC cells, whereas overexpression NPTX1 reversed the impact of overexpression miR-486-3p. Silencing miR-486-3p or overexpression NPTX1 both attenuated the suppressive influence of β-elemene on the malignant behavior of ACC cells. Additionally, tumor growth was suppressed and apoptosis was induced in tumor cells in vivo by β-elemene. In conclusion, β-elemene reduces ACC cell viability, hinders proliferation and migration, and induces apoptosis through the miR-486-3p/NPTX1 axis.
Insights
β-elemene inhibits adrenocortical carcinoma (ACC) progression by decreasing cell viability and migration while promoting apoptosis. This occurs through the miR-486-3p/NPTX1 pathway, highlighting a potential therapeutic mechanism for ACC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy.
- The therapeutic potential of β-elemene, known for its anti-inflammatory and antitumor properties, in ACC remains largely unexplored.
- Understanding the molecular mechanisms underlying β-elemene's effects on ACC is crucial for developing novel treatment strategies.
Purpose of the Study:
- To investigate the influence of β-elemene on the malignant progression of ACC.
- To elucidate the underlying molecular mechanism of β-elemene action in ACC.
- To explore the role of the miR-486-3p/NPTX1 axis in β-elemene's anti-ACC effects.
Main Methods:
- Cell viability, proliferation, migration, and apoptosis were assessed using CCK-8, clone formation, Transwell, wound healing, and flow cytometry assays.
- Quantitative real-time PCR (RT-qPCR) and Western blot were employed to analyze miR-486-3p and neuronal pentraxin 1 (NPTX1) expression.
- In vivo studies utilized a subcutaneous graft tumor model in mice to evaluate β-elemene's efficacy.
Main Results:
- β-elemene significantly reduced ACC cell viability, proliferation, and migration, while inducing apoptosis in vitro and suppressing tumor growth in vivo.
- β-elemene treatment upregulated miR-486-3p expression and downregulated NPTX1 expression in ACC cells.
- Experimental manipulation of miR-486-3p and NPTX1 levels confirmed their involvement in mediating β-elemene's anti-ACC effects.
Conclusions:
- β-elemene exerts significant anti-cancer effects against adrenocortical carcinoma by inhibiting cell viability, proliferation, and migration, and promoting apoptosis.
- The therapeutic mechanism involves the regulation of the miR-486-3p/NPTX1 axis, where β-elemene enhances miR-486-3p and suppresses NPTX1.
- These findings suggest that β-elemene, acting via the miR-486-3p/NPTX1 pathway, represents a promising therapeutic agent for adrenocortical carcinoma.
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