Rhamnetin induces sensitization of hepatocellular carcinoma cells to a small molecular kinase inhibitor or chemotherapeutic agents

Jia, Hui; Yang, Qian; Wang, Tao; Cao, Yu; Jiang, Qiyu; Ma, Haile; Sun, Hongbin; Hou, Mingxiao; Yang, Yongping; Feng, Fan

doi:10.1016/j.bbagen.2016.04.007

Cited by 103 publications

(104 citation statements)

References 36 publications

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“…GSEA showed that Notch signaling and JAK-STAT3 signaling were significantly activated in the patients with pre- miR-146a /C. Notch signaling may be involved in cell-fate decision and promote cell survival or anti-apoptosis by mediating the expression of some anti-apoptosis or pro-survival proteins [31,32]. Notch signaling also mediates the epithelial-mesenchymal transition process, leading to metastasis [31] and has been traditionally implicated as a key mechanism for the initiation and progression in CRC [33].…”

Section: Discussionmentioning

confidence: 99%

miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis

et al. 2016

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miR-146a plays important roles in cancer as it directly targets NUMB, an inhibitor of Notch signaling. miR-146a is reportedly regulated by a G>C polymorphism (SNP; rs2910164). This polymorphism affects various cancers, including colorectal cancer (CRC). However, the clinical significance of miR-146a polymorphism in CRC remains unclear. A total of 59 patients with CRC were divided into 2 groups: a CC/CG genotype (n = 32) and a GG genotype (n = 27), based on the miR-146a polymorphism. cDNA microarray analysis was performed using 59 clinical samples. Significantly enriched gene sets in each genotype were extracted using GSEA. We also investigated the association between miR-146a polymorphism and miR-146a, NUMB expression or migratory response in CRC cell lines. The CC/CG genotype was associated with significantly more synchronous liver metastasis (p = 0.007). A heat map of the two genotypes showed that the expression profiles were clearly stratified. GSEA indicated that Notch signaling and JAK/STAT3 signaling were significantly associated with the CC/CG genotype (p = 0.004 and p = 0.023, respectively). CRC cell lines with the pre-miR-146a/C revealed significantly higher miR-146a expression (p = 0.034) and higher NUMB expression and chemotactic activity. In CRC, miR-146a polymorphism is involved in liver metastasis. Identification of this polymorphism could be useful to identify patients with a high risk of liver metastasis in CRC.

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Section: Discussionmentioning

confidence: 99%

miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis

et al. 2016

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“…For the subcutaneous tumor model, MHCC97-H cells, which were infected with control or siCPNE3, were injected into nude mice. The in vivo experiments were conducted according to the protocol described earlier 21,22. Mice received solvent control phosphate buffer saline (PBS) or sorafenib (1.5 mg/kg) treatment.…”

Section: Methodsmentioning

confidence: 99%

Silencing the expression of copine-III enhances the sensitivity of hepatocellular carcinoma cells to the molecular targeted agent sorafenib

Chen

Jiang

Zhang

2018

CMAR

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BackgroundThe application of the oral targeted therapeutic agent sorafenib provides new hope for patients suffering from advanced stages of hepatocellular carcinoma (HCC), but the prognosis of such patients remains poor due to the rapid development of the multidrug resistance process in cancer pathogenesis. The present work evaluated whether copine-III, a novel cancer regulator encoded by the CPNE3 gene, would be a potential indicator of sorafenib resistance in HCC treatment.Materials and methodsThe endogenous expression of copine-III in clinical specimens was examined by quantitative polymerase chain reaction. Copine-III siRNA was transfected into HCC cells to downregulate copine-III expression. The effect of copine-III on sorafenib’s antitumor activation was identified by in vitro and in vivo experiments (MTT, Transwell, and flow cytometry as well as a nude mice model).ResultsHigh levels of copine-III in clinical specimens are related to poor prognosis of advanced HCC patients on sorafenib treatment. Infection of Ad-siCPNE3 significantly decreased the endogenous expression of copine-III and enhanced the susceptibility of MHCC97-H cells to sorafenib: the IC50 value decreased from 1.15±0.11 to 0.25±0.05 μmol/L. Moreover, silencing copine-III enhanced the effect of sorafenib on apoptosis, in vitro invasion/migration, and subcutaneous or intrahepatic growth of MHCC97-H cells in nude mice.ConclusionCopine-III is a novel potential indicator of prognosis for patients who received sorafenib for advanced HCC treatment.

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“…Similarly, miR‐34a is a negative regulator of the neurogenic locus Notch homolog protein 1 precursor (NOTCH‐1) signaling pathway and may be involved in increasing sorafenib sensitivity. The Notch‐1 signaling pathway promotes cell survival and impedes apoptotic signals, and increased expression of the same is said to reduce sorafenib activity . Additionally, the same miRNA was shown to target B‐cell lymphoma 2 and sensitize human HCC cells to sorafenib treatment .…”

Section: Micrornas Influencing Sorafenib Response and Their Mechanismmentioning

confidence: 99%

“…Certain nutrients and chemicals have been shown to enhance the expression of certain miRNAs, which in turn can increase the sorafenib response. Rhamnetin, a flavonoid from sea buckthorn, acts as a promising sensitizer of sorafenib and overcomes multidrug resistance in HCC by regulating miR‐34 and NOTCH‐1 expression . Chemical compounds such as PD407824 (wee1‐kinase inhibitor) and ellipticine (DNA topoisomerase inhibitor) were used in Hep3B cells to enhance miR‐122 and increase sorafenib sensitivity .…”

Section: Therapeutic Potential Of Mirnasmentioning

confidence: 99%

Sorafenib response in hepatocellular carcinoma: MicroRNAs as tuning forks

Kanthaje

Makol

Chakraborti

2017

Hepatology Research

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Hepatocellular carcinoma (HCC) is the primary liver malignancy that contributes towards the second most common cause of cancer‐related mortality. The targeted chemotherapeutic agent, sorafenib, is known to show a statistically significant but limited overall survival advantage in advanced HCC. However, the individual patient response towards sorafenib varies drastically, with most experiencing stable disease and few with partial response; complete response is very rare. Progressive disease despite the treatment is also evident in many patients, indicating drug resistance. These varied responses have been linked with the modulation of several intracellular signaling pathways. Notably, the regulation of these pathways through diverse operating biomolecules, including microRNAs (miRNAs), is the focus of recent studies. MicroRNAs are tiny, non‐coding RNA molecules that regulate the expression of several target genes. In addition, miRNAs are known to play a role in the progression of HCC carcinogenesis. Interestingly, miRNAs have also been identified to play differential roles in terms of sorafenib response in HCC such as biomarkers and functional modulation of cellular response to sorafenib, hence, they are also being therapeutically evaluated. This review outlines the role of reported miRNAs in different aspects of sorafenib response in HCC.

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Rhamnetin induces sensitization of hepatocellular carcinoma cells to a small molecular kinase inhibitor or chemotherapeutic agents

Cited by 103 publications

References 36 publications

miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis

miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis

Silencing the expression of copine-III enhances the sensitivity of hepatocellular carcinoma cells to the molecular targeted agent sorafenib

Sorafenib response in hepatocellular carcinoma: MicroRNAs as tuning forks

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