β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling

Cao, Zhang-Qi; Wang, Xuexi; Lü, Li; Xu, Jingwen; Li, Xiaobin; Zhang, Guang-ru; Ma, Zhanjun; Shi, Anchen; Wang, Yan; Song, Yujun

doi:10.3389/fphar.2018.01525

Cited by 51 publications

(29 citation statements)

References 51 publications

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“…Furthermore, BRG1 has been reported as a corepressor of ZEB1 to regulate E-cadherin transcription and was required for the induction of EMT by ZEB1 24. It has been reported that activation of both Akt and other signaling pathways may induce EMT contributing to tumor metastasis 39. A recent study described that BRG1 acted as a prognostic indicator and a potential therapeutic target for PCa 40.…”

Section: Discussionmentioning

confidence: 99%

HMGB1 Promotes Prostate Cancer Development and Metastasis by Interacting with Brahma-Related Gene 1 and Activating the Akt Signaling Pathway

Song

Huang

et al. 2019

Theranostics

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Background and Aim : We have previously shown that high-mobility group box 1 ( HMGB1 ) is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of HMGB1 in tumor development and progression remains largely unknown. In this study, we investigated the molecular mechanisms of HMGB1 in PCa tumorigenesis. Methods : Gain-of-function and loss-of-function experiments were used to determine the biological functions of HMGB1 both in vitro and in vivo . Bioinformatic analysis, immunoprecipitation, and immunofluorescence assays were applied to discern and examine the relationship between HMGB1 and its potential targets. Specimens from 64 patients with PCa were analyzed for the expression of HMGB1 and its relationship with Brahma-related gene 1 ( BRG1 ) was examined by immunohistochemistry. Results : The results demonstrated that ectopic expression of HMGB1 facilitated growth and metastasis of PCa by enhancing Akt signaling pathway and promoting epithelial-mesenchymal transition (EMT), while silencing of HMGB1 showed the opposite effects. Mechanistically, HMGB1 exerted these functions through its interaction with BRG1 which may augment BRG1 function and activate the Akt signaling pathway thereby promoting EMT. Importantly, both HMGB1 and BRG1 expression was markedly increased in human PCa tissues. Conclusions : Taken together, these findings indicate that upregulation of HMGB1 promotes PCa development via activation of Akt and accelerates metastasis through regulating BRG1 -mediated EMT. HMGB1 could be used as a novel potential target for the treatment of PCa.

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Section: Discussionmentioning

confidence: 99%

HMGB1 Promotes Prostate Cancer Development and Metastasis by Interacting with Brahma-Related Gene 1 and Activating the Akt Signaling Pathway

Song

Huang

et al. 2019

Theranostics

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“…According the Herbs-Compounds network, we found the four hub compounds: beta-sitosterol, sitosterol, kaempferol and Stigmasterol. Among of them, beta-sitosterol has shown potent anti-pancreatic cancer activity by effectively inhibited the growth of tumor cell lines by inhibiting proliferation [39]. Kaempferol is a flavonoid, has antioxidant and anti-pancreatic cancer effect by inhibiting pancreatic cancer cell growth via PI3K/AKT pathway [40].…”

Section: Discussionmentioning

confidence: 99%

Utilising network pharmacology to explore the underlying mechanism of Wumei Pill in treating pancreatic neoplasms

Wan

Liu

et al. 2019

BMC Complement Altern Med

101

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Background Wumei Pill (WMP), a famous herbal formula, has been widely used to treat digestive system diseases in clinical practice in China for centuries. We have found a correlation between the indications of WMP and the typical symptoms of pancreatic neoplasms. However, the pharmacological mechanisms of WMP still remain unknown. Methods In the present work, we used a network pharmacological method to predict its underlying complex mechanism of treating pancreatic neoplasms. Firstly, we obtained relative compounds of WMP based on TCMSP database, TCM database@Taiwan and TCMID database and collected potential targets of these compounds by target fishing. Then we built the pancreatic neoplasms target database by CTD, TTD, PharmGKB. Based on the matching results between WMP potential targets and pancreatic neoplasms targets, we built a PPI network to analyze the interactions among these targets and screen the hub targets by topology. Furthermore, DAVID bioinformatics resources were utilized for the enrichment analysis on GO_BP and KEGG. Results A total of 80 active ingredients and 77 targets of WMP were picked out. The results of DAVID enrichment analysis indicated that 58 cellular biological processes (FDR < 0.01) and 17 pathways (FDR < 0.01) of WMP mostly participated in the complex treating effects associated with proliferation, apoptosis, inflammatory response and angiogenesis. Moreover, 17 hub nodes of WMP (PTGS2, BCL2, TP53, IL6, MAPK1, EGFR, EGF, CASP3, JUN, MAPK8, MMP9, VEGFA, TNF, MYC, AKT1, FOS and TGFB1) were recognized as potential targets of treatments, implying the underlying mechanisms of WMP acting on pancreatic neoplasms. Conclusion WMP could alleviate the symptoms of pancreatic neoplasms through the molecular mechanisms predicted by network pharmacology. This study proposes a strategy to elucidate the mechanisms of Traditional Chinese Medicine (TCM) at the level of network pharmacology. Electronic supplementary material The online version of this article (10.1186/s12906-019-2580-y) contains supplementary material, which is available to authorized users.

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“…9). From the network, it was observed that RELA and NFKB1 had the largest degree (19). The other genes with large degrees were IKBKG, JUN, MAPK1, AKT1, and TP53 (17, 16, 15, 12, and 10, respectively).…”

Section: Gene-pathway Networkmentioning

confidence: 99%

Network Pharmacology-based Elucidation of Molecular Biological Mechanisms of Kanglaite Injection for Treatment of Pancreatic Ductal Adenocarcinoma

Dan

et al. 2020

Preprint

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Background: Kanglaite injection (KLTi) has shown good clinical efficacy in the treatment of pancreatic ductal adenocarcinoma (PDAC). However, its molecular biological mechanisms are still unclear. This study used network pharmacology approach to investigate the molecular biological mechanisms of KLTi.Methods: Compounds in KLTi were screened using TCMSP and drug targets were obtained from the DRUGBANK. Next, the GEO database was searched for differentially expressed genes in cancerous tissues and healthy tissues of PDAC patients to identify targets. Subsequently, the protein-protein interaction data of KLTi and PDAC targets were constructed by BisoGenet. A visual analysis was done to extract KLTi candidate genes for PDAC. The candidate genes were enriched using GO and KEGG by Metascape, and the gene-pathway network was constructed to further screen the key genes.Results: A total of 10 active compounds and 36 drug targets were screened for KLTi, 919 differentially expressed genes associated with PDAC were identified from GEO, and 139 KLTi candidate genes against PDAC were excavated by BisoGenet. The gene-pathway network showed RELA, NFKB1, IKBKG, JUN, MAPK1, TP53, and AKT1 as the core genes, predicting that KLTi intervenes in PDAC by acting on these genes.Conclusions: Our study suggested that KLTi plays an anti-PDAC role by intervening in the cell cycle, inducing apoptosis, regulating protein binding, inhibiting nerve invasion, and down-regulating the NF-κB, MAPK, and PI3K-Akt signaling pathways. In addition, it might also directly participate in the pancreatic cancer pathway. These results provide new evidence and therapeutic direction for subsequent clinical applications and basic research on KLTi in PDAC.

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β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling

Cited by 51 publications

References 51 publications

HMGB1 Promotes Prostate Cancer Development and Metastasis by Interacting with Brahma-Related Gene 1 and Activating the Akt Signaling Pathway

HMGB1 Promotes Prostate Cancer Development and Metastasis by Interacting with Brahma-Related Gene 1 and Activating the Akt Signaling Pathway

Utilising network pharmacology to explore the underlying mechanism of Wumei Pill in treating pancreatic neoplasms

Network Pharmacology-based Elucidation of Molecular Biological Mechanisms of Kanglaite Injection for Treatment of Pancreatic Ductal Adenocarcinoma

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