Asiatic Acid Interferes with Invasion and Proliferation of Breast Cancer Cells by Inhibiting WAVE3 Activation through PI3K/AKT Signaling Pathway
Autor: | Hong-yu Chen, Li-min Zhang, Wen-li Chen, Li-sheng Chang, Qin Shi, Xiao-jun Gou, Mei-xiang Zhou, Huan-huan Bai, Ming-ming Ding, Qi Shi, Li-wei Liu |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Article Subject
Breast Neoplasms General Biochemistry Genetics and Molecular Biology Flow cytometry Metastasis Mice Phosphatidylinositol 3-Kinases Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness PI3K/AKT/mTOR pathway Cell Proliferation General Immunology and Microbiology medicine.diagnostic_test Akt/PKB signaling pathway Cell growth Chemistry General Medicine Transfection medicine.disease Xenograft Model Antitumor Assays Wiskott-Aldrich Syndrome Protein Family Gene Expression Regulation Neoplastic Oncogene Protein v-akt Mechanism of action Apoptosis Cancer research Medicine Female medicine.symptom Pentacyclic Triterpenes Research Article Signal Transduction |
Zdroj: | BioMed Research International, Vol 2020 (2020) BioMed Research International |
ISSN: | 2314-6141 2314-6133 |
Popis: | Objective. To explore the ability of asiatic acid to interfere with the invasion and proliferation of breast cancer cells by inhibiting WAVE3 expression and activation through the PI3K/AKT signaling pathway. Methods. The MDA-MB-231 cells with strong invasiveness were screened by transwell assay, and plasmids with high expression of WAVE3 were constructed for transfection. The transfection effect and protein expression level of plasmids were verified by PCR and WB. The effects of asiatic acid on cell proliferation and invasion were investigated by flow cytometry. The xenografted tumor models in nude mice were established to study the antitumor activity of asiatic acid. Results. Asiatic acid significantly inhibited the activity of MDA-MB-231 cells, and the expression level of WAVE3 increased significantly in the tissue of ductal carcinoma in situ and was lower than that in the metastasis group. After plasmid transfection, the mRNA and protein expression of WAVE3 increased significantly in the cells. Asiatic acid at different concentrations had an impact on cell apoptosis and invasion and could significantly inhibit the expression of WAVE3, P53, p-PI3K, p-AKT, and other proteins. The T/C(%) of asiatic acid (50 mg/kg) for MDA-MB-231(F10) xenografted tumor in nude mice was 46.33%, with a tumor inhibition rate of 59.55%. Asiatic acid could significantly inhibit the growth of MDA-MB-231 (F10) xenografted tumors in nude mice (p<0.05). Conclusions. Asiatic acid interferes with the ability of breast cancer cells to invade and proliferate by inhibiting WAVE3 expression and activation and the mechanism of action may be related to the PI3K/AKT signaling pathway. |
Databáze: | OpenAIRE |
Externí odkaz: |