The Chinese Medicine, Jiedu Recipe, Inhibits the Epithelial Mesenchymal Transition of Hepatocellular Carcinoma via the Regulation of Smad2/3 Dependent and Independent Pathways

Liang, Shufang; Zou, Yong; Gao, Jingdong; Liu, Xiaolin; Lin, Wanfu; Yin, Zifei; Du, Juan; Zhang, Yani; Chen, Qun-wei; Li, Shu; Cheng, Baohua; Ling, Changquan

doi:10.1155/2018/5629304

Cited by 12 publications

(8 citation statements)

References 23 publications

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“…[ 7,8 ] Recent developments in molecular and cell biology have led to significant insights into the biological functions of CHM and have shown that some medicines can inhibit tumor cell invasion, metastasis, angiogenesis, and the epithelial–mesenchymal transition and induce cell death. [ 9,10 ]…”

Section: Introductionmentioning

confidence: 99%

Scutebarbatine A induces cytotoxicity in hepatocellular carcinoma via activation of the MAPK and ER stress signaling pathways

Feng

et al. 2021

J Biochem & Molecular Tox

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Scutebarbatine A (SBT‐A), a diterpenoid alkaloid found in the root of Scutellaria barbata D. Don, has been reported to induce the apoptosis of A549 cells. In this study, we investigated the antitumor activity of SBT‐A in human hepatocellular carcinoma (HCC) cells and the potential underlying mechanisms. Our results showed that SBT‐A inhibited the growth of HCC cells in a dose‐dependent manner. SBT‐A treatment caused cell cycle arrest and decreased the expression of cyclin B1, cyclin D1, p‐Cdc2, and p‐Cdc25C. SBT‐A triggered cell apoptosis via a caspase‐dependent pathway, and cell viability was partially restored by pretreatment with the pan‐caspase inhibitor Z‐VAD‐FMK. In HCC cells, treatment with SBT‐A increased the phosphorylation of extracellular signal‐regulated kinase 1 and 2 (ERK1/2), c‐Jun N‐terminal kinase 1 and 2 (JNK1/2), and p38 mitogen‐activated protein kinase (p38 MAPK). Moreover, SBT‐A activated endoplasmic reticulum (ER) stress through the upregulation of protein kinase RNA‐like ER kinase (PERK), activating transcription factor 4 (ATF‐4), and CCAAT‐enhancer‐binding protein (C/EBP) homologous protein (CHOP). Our data indicate that SBT‐A inhibits the proliferation of HCC cells and triggers their apoptosis via the activation of MAPK and ER stress. SBT‐A is a potential agent for the treatment of HCC.

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Section: Introductionmentioning

confidence: 99%

Scutebarbatine A induces cytotoxicity in hepatocellular carcinoma via activation of the MAPK and ER stress signaling pathways

Feng

et al. 2021

J Biochem & Molecular Tox

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“…3 At present, surgical resection is the best treatment strategy for HCC. 4 However, the outcomes of patients with HCC remain unsatisfactory due to late diagnosis, distant metastasis, and high recurrence rate. 5 Traditional Chinese medicine (TCM), a hot spot for tumor treatment, has several advantages, and has been widely used for the treatment of diverse cancer types in China.…”

Section: Introductionmentioning

confidence: 99%

<p>Traditional Chinese Medicine Xiaoai Jiedu Recipe Suppresses the Development of Hepatocellular Carcinoma via Regulating the microRNA-29a/Signal Transducer and Activator of Transcription 3 Axis</p>

Shi

Kong

et al. 2020

OTT

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Objective: Hepatocellular carcinoma (HCC) is one of the most frequent and lethal tumors affecting human health worldwide. The aim of this study was to investigate the anti-cancer effects of Xiaoai Jiedu Recipe (XJR) on HCC development and its underlying mechanisms. Methods: The expression of microRNA-29a (miR-29a) and signal transducer and activator of transcription 3 (STAT3) in HCC tissues and cells was determined by quantitative real-time polymerase chain reaction. The proliferation, migration, and invasion of HCC cells were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, woundhealing, and transwell assays, respectively. The regulatory relationship between miR-29a and STAT3 in HCC was predicted by TargetScan and analyzed by luciferase reporter and RNA pull-down assays. The protein expression of matrix metalloproteinase (MMP)-2/9 and STAT3 was detected by Western blotting. A xenograft tumor mouse model was established, and tumor weight and volume were measured. Results: The expression of miR-29a was significantly decreased in HCC tissues and cells compared with that in normal tissues and cells. The up-regulation of miR-29a was related with lymph node metastasis and tumor node metastasis stage. XJR treatment significantly increased the expression of miR-29a, decreased cell viability, migration, and invasion, and reduced the protein expression of MMP-2/9 in HCC cells in a concentration-dependent manner. The anti-tumor effect of XJR on HCC cells was reversed by treatment with miR-29a inhibitor. STAT3 was predicted as a target of miR-29a, and its expression was negatively regulated by miR-29a. Moreover, STAT3 knockdown suppressed the malignant behavior of HCC cells, and its anti-tumor function was reversed by treatment with miR-29a inhibitor. Furthermore, XJR treatment inhibited tumor growth in mice through elevating miR-29a expression and inhibiting STAT3 expression. Conclusion: XJR suppressed the development of HCC via regulating miR-29a and STAT3.

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“…And the findings suggest that RvD1 inhibits cell proliferation and the expression of inflammatory cytokines in LPS-treated liver cancer cells by targeting the MAPK pathway in HepG2 cells 25 . TGFβ1 treatment increased the phosphorylation of Smad2/3, p38 MAPK, JNK, ERK1/2, and Akt in SMMC-7721 cells and pretreatment with JR blocked TGFβ1-induced activation of Smad2/3 and Akt and MAPKs in HCC 37 . But in other research, Puerarin inhibited proliferation of SMMC-7721 cells and promoted their apoptosis in a dose- and time-dependent fashion (p < 0.05).…”

Section: Discussionmentioning

confidence: 90%

miR-302a inhibits human HepG2 and SMMC-7721 cells proliferation and promotes apoptosis by targeting MAP3K2 and PBX3

Wang

Jiang

et al. 2019

Sci Rep

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Hepatocellular carcinoma (HCC) is the most common liver cancer and has a poor prognosis. miR-302a is an important regulator of tumor occurrence and deterioration, while MAP3K2 and PBX3 genes are involved in cancer cell proliferation and apoptosis. In this study, the expression of miR-302a and MAP3K2/PBX3 were evaluated by qPCR in liver cancer cell lines. Next, the target relationship between miR-302a and MAP3K2/PBX3 was verified using luciferase assays. Meanwhile, the expression correlation between miR-302a and target genes was analyzed in cancer tissue and para-cancerous tissue. In addition, an increased miR-302a level in HepG2 cells and SMMC-7721 cells were achieved through transfection with miR-302a mimics, and the effects on HepG2 cell and SMMC-7721 cell proliferation, apoptosis and MAPK pathways were determined using MTT, flow cytometry, qPCR and western blot assays. The results showed that liver cancer cell lines exhibited low miR-302a expression and MAP3K2 and PBX3 were confirmed to be the target genes of miR-302a. Meanwhile, the HE results showed that cells became enlarged with loose cytoplasm and formed balloon-like lesions in HCC specimens and we found a significant negative correlation between miR-302a and MAP3K2/PBX3 expression. In addition, treatment with miR-302a mimics inhibited HepG2 cells and SMMC-7721 cells proliferation and increased the apoptosis rate. Further research revealed that the MAPK key factors p-p38, p-ERK1/2 and p-JNK were significantly reduced in miR-302a transfected cells and MAP3K2/PBX3 silenced cells. Besides, MAP3K2 and PBX3 overexpression in miR-302a mimics-treated cells exerted the opposite effects. In conclusion, miR-302a inhibited proliferation and promoted apoptosis in human hepatoma cells by targeting MAP3K2 and PBX3.

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The Chinese Medicine, Jiedu Recipe, Inhibits the Epithelial Mesenchymal Transition of Hepatocellular Carcinoma via the Regulation of Smad2/3 Dependent and Independent Pathways

Cited by 12 publications

References 23 publications

Scutebarbatine A induces cytotoxicity in hepatocellular carcinoma via activation of the MAPK and ER stress signaling pathways

Scutebarbatine A induces cytotoxicity in hepatocellular carcinoma via activation of the MAPK and ER stress signaling pathways

<p>Traditional Chinese Medicine Xiaoai Jiedu Recipe Suppresses the Development of Hepatocellular Carcinoma via Regulating the microRNA-29a/Signal Transducer and Activator of Transcription 3 Axis</p>

miR-302a inhibits human HepG2 and SMMC-7721 cells proliferation and promotes apoptosis by targeting MAP3K2 and PBX3

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