Triptolide Suppresses Growth of Breast Cancer by Targeting HMGB1 &lt;i&gt;in Vitro&lt;/i&gt; and &lt;i&gt;in Vivo&lt;/i&gt;

Jiang, Wei; Chen, Maojian; Xiao, Chanchan; Yang, Weiping; Qin, Qinghong; Tan, Qingyuan; Liang, Zheng; Mao, Anyun; Wei, Changyuan

doi:10.1248/bpb.b18-00818

Cited by 38 publications

(29 citation statements)

References 45 publications

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“…HMGB1 is reported to be highly expressed in many malignant tumours and is closely related to apoptosis, proliferation and migration of cancer cells [3,13]. Therefore, anticancer therapy targeting HMGB1 is attracting increased attention [20,21].…”

Section: Discussionmentioning

confidence: 99%

High mobility group box 1 regulates gastric cancer cell proliferation and migration via RAGE-mTOR/ERK feedback loop

Tang¹,

Wang²,

Cai

et al. 2021

J. Cancer

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Gastric cancer (GC) is a common malignancy tumour in China. Despite various therapeutic approaches to improve the survival rate of GC patients, the effectiveness of currently available treatments remains unsatisfactory. High mobility group box 1 (HMGB1) is reported to play a role in tumour development. However, the molecular mechanisms involved in HMGB1-mediated regulation of proliferation and migration of GC cells remain unclear. In the present study, we demonstrated that HMGB1 is highly expressed in GC cells and tissue. In HGC-27 GC cells, HMGB1 overexpression or HMGB1 RNA interference both demonstrated that HMGB1 could promote GC cell proliferation and migration. Investigation of the underlying molecular mechanisms revealed that HMGB1 enhanced cyclins expression, induced epithelial-to-mesenchymal transition and matrix metalloproteinase (MMPs) expression and promoted RAGE expression as well as RAGE-mediated activation of Akt/mTOR/P70S6K and ERK/P90RSK/CREB signalling pathways. We also found that inhibition of ERK and mTOR using specific inhibitors reduced recombinant human HMGB1-induced RAGE expression, suggesting that the RAGE-mTOR/ERK positive feedback loop is involved in HMGB1-induced GC cell proliferation and migration. Our study highlights a novel mechanism by which HMGB1 promotes GC cell proliferation and migration via RAGE-mediated Akt-mTOR and ERK-CREB signalling pathways which also involves the RAGE-mTOR/ERK feedback loop. These findings indicate that HMGB1 is a potential therapeutic target for GC.

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Section: Discussionmentioning

confidence: 99%

High mobility group box 1 regulates gastric cancer cell proliferation and migration via RAGE-mTOR/ERK feedback loop

Tang¹,

Wang²,

Cai

et al. 2021

J. Cancer

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“…TPL has been shown to have potent antitumor activity in various preclinical cancer models [8], such as lung cancer, breast cancer and pancreatic cancer [32][33][34]. However, the effect of TPL on MF was still unclear.…”

Section: Discussionmentioning

confidence: 99%

Triptolide Inhibits the Activation of NLRP3 Inflammasome by Inhibiting NF-κB Pathway and Improves Myocardial Fibrosis

Shen

Wang

2021

Preprint

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ObjectiveTriptolide (TPL) is identified to be involved in the treatment for myocardial fibrosis (MF). This study investigated the mechanism of TPL in MF in rats and observed its effect on NLRP3 inflammasome signaling pathway.Materials and MethodsThe MF rat model was established by subcutaneous injection of isoproterenol (ISO), and treated by subcutaneous injection of TPL. After modeling for 1 week, the cardiac function of rats was evaluated, including LVEF, LVFS, LVES, LVED LVIDs and LVPWs. The HMI and LVMI were measured. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM-1), and NLRP3 inflammasome factors (NLRP3, ASC, caspase-1) in rats were detected. HE staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats.ResultsLVED, LVES, LVIDs and LVPWs of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, HMI and LVMI were upregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF.ConclusionsTPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved the degree of MF in MF rats.

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“…Evidence has been shown that HMGB1 can activate the TLR4/NF-kB signaling pathway, which promotes tumor cell proliferation, migration and invasion. 33 In addition, kang et al indicated that HMGB1 could induce the phosphorylation of p38 and JNK in leukemic cells. 34 Thus, we analyzed NF-kB p65, p38 and JNK, which are 3 key factors involved in tumor development and progression.…”

Section: Discussionmentioning

confidence: 99%

DARS-AS1 Knockdown Inhibits the Growth of Cervical Cancer Cells via Downregulating HMGB1 via Sponging miR-188-5p

Zhu

Han

2020

Technol Cancer Res Treat

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Background: Evidence has been shown that long noncoding RNAs (lncRNAs) play an important role in the development of cervical cancer. Recently, lncRNA DARS-AS1 was shown to be dysregulated in several cancer types, but the role of DARS-AS1 in cervical cancer remains unclear. Methods: Immunofluorescence staining, flow cytometry and transwell invasion assays were used to determine proliferation, apoptosis and invasion in cervical cancer cells, respectively. The dual luciferase reporter system assay was performed to assess the interaction between DARS-AS1, miR-188-5p, and high mobility group box 1 (HMGB1) in cervical cancer cells. Results: Downregulation of DARS-AS1 markedly inhibited the proliferation and invasion of cervical cancer cells. Moreover, DARS-AS1 knockdown obviously induced the apoptosis of SiHa and HeLa cells. Meanwhile, luciferase reporter assay identified that miR-188-5p was the potential miRNA binding of DARS-AS1, and HMGB1 was the potential binding target of miR-188-5p. Mechanistic analysis indicated that downregulation of DARS-AS1 decreased the expression of HMGB1 by acting as a competitive “sponge” of miR-188-5p. Conclusion: In this study, we found that DARS-AS1 knockdown suppressed the growth of cervical cancer cells via downregulating HMGB1 via sponging miR-188-5p. Therefore, DARS-AS1 might serve as a potential target for the treatment of cervical cancer.

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Triptolide Suppresses Growth of Breast Cancer by Targeting HMGB1 <i>in Vitro</i> and <i>in Vivo</i>

Cited by 38 publications

References 45 publications

High mobility group box 1 regulates gastric cancer cell proliferation and migration via RAGE-mTOR/ERK feedback loop

High mobility group box 1 regulates gastric cancer cell proliferation and migration via RAGE-mTOR/ERK feedback loop

Triptolide Inhibits the Activation of NLRP3 Inflammasome by Inhibiting NF-κB Pathway and Improves Myocardial Fibrosis

DARS-AS1 Knockdown Inhibits the Growth of Cervical Cancer Cells via Downregulating HMGB1 via Sponging miR-188-5p

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