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Magnesium cantharidate inhibits hepatocellular cancer by targeting RACK1
Da Sun1, Xiaofei Li1,2, Meichen Liu1
1College of Basic Medicine, Zunyi Medical University Zunyi 563000, Guizhou, China.
Objective:
The aim of this study was to investigate whether magnesium cantharidate (MC) exerts anti-hepatocellular carcinoma (anti-HCC) effects by targeting receptor for activated C kinase 1 (RACK1).
Methods:
The Cancer Genome Atlas (TCGA) database was used to analyze the expression of RACK1 in liver tissues. Molecular docking was used to examine the binding interactions between MC and RACK1. Huh-7 and SK-Hep-1 liver cancer cells' viability, proliferation, and apoptosis were assessed by using the Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry, respectively. RNA sequencing was used to explore the underlying mechanisms. Quantitative real-time PCR, immunohistochemistry, and western blotting were performed to explore the expression of key genes and proteins.
Results:
TCGA analysis revealed significant upregulation of RACK1 in liver cancer tissues that was correlated with tissue type, grade, TP53 mutation, and overall survival. Molecular docking results revealed that the minimum binding energy between MC and RACK1 was -5.8 kcal/mol. Moreover, RACK1 overexpression significantly promoted cell viability and proliferation, and inhibited apoptosis in liver cancer cells. However, MC significantly reversed the viability, proliferation, and apoptosis effects induced by RACK1 overexpression in liver cancer cells. MC significantly inhibited the growth of subcutaneously transplanted tumors in vivo. RNA sequencing revealed that MC inhibited proliferation and apoptosis by targeting RACK1 to regulate calcium ion transport, ion channels, and cell adhesion in liver cancer cells.
Conclusion:
MC exerts anti-HCC effects by targeting RACK1.
Insights
Magnesium cantharidate (MC) shows anti-hepatocellular carcinoma (anti-HCC) effects by targeting the receptor for activated C kinase 1 (RACK1). MC inhibits liver cancer cell growth and tumor development by regulating RACK1.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) is a major global health concern.
- Receptor for activated C kinase 1 (RACK1) is upregulated in liver cancer tissues.
- RACK1 overexpression promotes HCC cell viability and inhibits apoptosis.
Purpose of the Study:
- To investigate the anti-HCC effects of magnesium cantharidate (MC).
- To determine if MC targets RACK1 to exert its anti-cancer effects.
Main Methods:
- Analysis of RACK1 expression in The Cancer Genome Atlas (TCGA) database.
- Molecular docking to assess MC-RACK1 binding.
- In vitro assays (CCK-8, EdU, flow cytometry) on liver cancer cells.
- In vivo tumor growth inhibition studies.
- RNA sequencing to elucidate mechanisms.
Main Results:
- RACK1 upregulation in HCC tissues correlates with poor prognosis.
- MC binds to RACK1 and reverses RACK1-induced pro-cancer effects in vitro.
- MC inhibits tumor growth in vivo.
- MC targets RACK1 to regulate calcium ion transport, ion channels, and cell adhesion.
Conclusions:
- Magnesium cantharidate (MC) demonstrates significant anti-HCC activity.
- MC exerts its effects by specifically targeting RACK1.
- Targeting RACK1 with MC offers a potential therapeutic strategy for HCC.
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