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Actein Inhibits Tumor Growth and Metastasis in HER2-Positive Breast Tumor Bearing Mice via Suppressing AKT/mTOR and Ras/Raf/MAPK Signaling Pathways.

ABSTRACT: HER2-positive breast cancer accounts for 15-20% in breast cancer and 50% of the metastatic HER2-positive breast cancer patients died of central nervous system progression. The present study investigated the effects of actein (a natural cycloartane triterpene) on cells adhesion, migration, proliferation and matrix degradation, and its underlying mechanism in HER2-positive breast cancer cells. The in vivo effect of actein on tumor growth and metastasis in MDA-MB-361 tumor-bearing mice as well as the anti-brain metastasis in tail vein injection mice model were also investigated. Our results showed that actein inhibited HER2-positive breast cancer cells viability, proliferation and migration. Actein also induced MDA-MB-361 cells G1 phase arrest and inhibited the expressions of cyclins and cyclin-dependent kinases. For intracellular mechanisms, actein inhibited the expressions of molecules in AKT/mTOR and Ras/Raf/MAPK signaling pathways. Furthermore, actein (15 mg/kg) was shown to exhibit anti-tumor and anti-metastatic activities in MDA-MB-361 breast tumor-bearing mice, and reduced brain metastasis in tail vein injection mice model. All these findings strongly suggested that actein is a potential anti-metastatic agent for HER2-positive breast cancer.

SUBMITTER: Wu XX

PROVIDER: S-EPMC7269144 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Actein Inhibits Tumor Growth and Metastasis in HER2-Positive Breast Tumor Bearing Mice via Suppressing AKT/mTOR and Ras/Raf/MAPK Signaling Pathways.

Wu Xiao-Xiao XX Yue Grace Gar-Lee GG Dong Jin-Run JR Lam Christopher Wai-Kei CW Wong Chun-Kwok CK Qiu Ming-Hua MH Lau Clara Bik-San CB

Frontiers in oncology 20200527

HER2-positive breast cancer accounts for 15-20% in breast cancer and 50% of the metastatic HER2-positive breast cancer patients died of central nervous system progression. The present study investigated the effects of actein (a natural cycloartane triterpene) on cells adhesion, migration, proliferation and matrix degradation, and its underlying mechanism in HER2-positive breast cancer cells. The <i>in vivo</i> effect of actein on tumor growth and metastasis in MDA-MB-361 tumor-bearing mice as we ...[more]

PMID: 32547952

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Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most common clinical malignancies quite susceptible to recurrence and metastasis. Despite several improvements in therapeutic approaches, the prognosis remains poor due to the limited treatment options. A bioinformatics analysis based on TCGA databases revealed that the recombinant human L antigen family member 3 (LAGE3) might function as an effective prognostic and diagnostic biomarker for HCC, as LAGE3, a protein-coding gene, maintains several important biological functions and has a physiological significance in the CTAG family while simultaneously being involved in regulating the occurrence and invasion of numerous types of tumors. However, the LAGE3 gene's functional and regulatory mechanism in the progression of HCC remains unclear.MethodsThe LAGE3 level was investigated in 79 HCC tissues cases, ten HCC adjacent tissue cases, and six cases of normal liver tissues by IHC, while the LAGE3 level was evaluated in BEL-7404, SMCC-7721, Huh-7, HepG2, and MIHA cell lines by qRT-PCR and Western blot tests. Although the proliferation, migration, invasion, and apoptotic abilities of HCC cells were measured in vitro after silencing assay to probe the role of LAGE3 in HCC cells, the tumor xenograft growth experiment was used to verify the in vivo effect of LAGE3 gene knockdown on the growth of HCC tumors combined with bioinformatics analysis to study the LAGE3 mechanisms regulating HCC proliferation.ResultsOur results implied that LAGE3 was extensively expressed in HCC cell lines like BEL-7404, SMCC-7721, and Huh-7 cells as well as HCC tissues, but a lower expression was observed in HepG2 cells. Additionally, LAGE3 restrains cellular proliferation, promotes apoptotic pathways in HCC cells, and inhibits the growth of HCC tumors in vivo. Lastly, it was stated that LAGE3 might promote tumor development in HCC via PI3K/AKT/mTOR and Ras/RAF/MAPK pathways.ConclusionThis study shows that the development of specific LAGE3 target drugs might become new effective treatment modalities for HCC patients.

Dataset Information

Actein Inhibits Tumor Growth and Metastasis in HER2-Positive Breast Tumor Bearing Mice via Suppressing AKT/mTOR and Ras/Raf/MAPK Signaling Pathways.

Publications

Actein Inhibits Tumor Growth and Metastasis in HER2-Positive Breast Tumor Bearing Mice via Suppressing AKT/mTOR and Ras/Raf/MAPK Signaling Pathways.

Similar Datasets

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