Mitogen-activated protein kinases in hepatocellular carcinoma development

Min, Lihua; He, Baokun; Hui, Lijian

doi:10.1016/j.semcancer.2010.10.011

Cited by 168 publications

(147 citation statements)

References 154 publications

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“…Vitamin D 3 exhibits several antiinflammatory effects, including inhibition of p38 stress kinase signaling and the subsequent production of proinflammatory cytokines (14). P38, a member of the MAPK family, has been reported to play a key role in the malignant transformation and is required for the invasive capacity of human hepatocellular carcinoma and HNSCC cell lines (40,41). The ability of calcitriol to reduce the production of proinflammatory cytokines, such as IL6, by inhibiting p38 signaling has been demonstrated in cancer cells (42).…”

Section: Discussionmentioning

confidence: 99%

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

Chen

Hsieh

et al. 2015

Molecular Cancer Therapeutics

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The aim of this study was to highlight the role of 1a,25-dihydroxyvitamin D3 (calcitriol) in esophageal squamous cell carcinoma (SCC). The human esophageal SCC cell lines CE81T and TE2 were selected for cellular and animal experiments to investigate the changes in tumor behavior after calcitriol supplementation and the underlying mechanisms. Moreover, we evaluated the relationship between calcitriol supplementation, myeloid-derived suppressor cell (MDSC) recruitment, IL6 levels, and tumor progression by a 4-nitroquinoline 1-oxide (4-NQO)-induced esophageal tumor animal model. In this study, we demonstrated that calcitriol supplementation inhibited aggressive tumor behavior both in vitro and in vivo. The underlying changes included increased cell death, a lower degree of epithelial-mesenchymal transition, and inhibited IL6 signaling. In the 4-NQOinduced esophageal tumor animal model, increased IL6 and MDSC recruitment were linked with invasive esophageal tumors. Supplementation with calcitriol attenuated the level of IL6, the induction of MDSCs, and the incidence of 4-NQO-induced invasive tumors. Moreover, the IL6-induced changes in C57 mice, including augmented MDSC recruitment, increased levels of ROS and p-Stat3 in MDSCs, and higher suppressive function of MDSCs in T-cell proliferation, which were abrogated by calcitriol supplementation. On the basis of our results, we concluded that calcitriol abrogated the IL6-induced aggressive tumor behavior and MDSC recruitment to inhibit esophageal tumor promotion. Therefore, we suggest that supplementation with vitamin D 3 may be a promising strategy for the prevention and treatment of esophageal SCC.

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Section: Discussionmentioning

confidence: 99%

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

Chen

Hsieh

et al. 2015

Molecular Cancer Therapeutics

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“…Several signal transduction pathways, including the PKC pathway and the MAPK pathway, are activated in response to a variety of external stimuli and have been demonstrated to be involved in a wide variety of cellular responses such as growth, differentiation, gene expression, and angiogenesis [27][28][29][30] . In VSMCs, the PKC-β2 isoform, but not PKC-α, has been shown to be activated in response to hyperglycemia.…”

Section: Discussionmentioning

confidence: 99%

Breviscapine inhibits high glucose-induced proliferation and migration of cultured vascular smooth muscle cells of rats via suppressing the ERK1/2 MAPK signaling pathway

Xue

et al. 2012

Acta Pharmacol Sin

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Aim: To investigate the influences of breviscapine, a flavonoid extracted from Erigeron breviscapus, on the proliferation and migration of vascular smooth muscle cells (VSMCs) cultured in a high glucose medium and the underlying mechanisms. Methods: VSMCs were isolated from thoracic aortas of male Sprague-Dawley rats and cultured in vitro. Cell proliferation was evaluated using Counting Kit-8 cell viability assay. Cell migration was evaluated using transwell migration assay and in vitro scratch assay. The expression and activity of protein kinase C-β2 (PKC-β2), extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38), and JNK mitogen-activated protein kinase (JNK) were measured with Western blotting. Results: Exposure of VSMCs to a high glucose (25 mmol/L) medium significantly increased the proliferation and migration potential as compared to the control group. Pretreatment with breviscapine (65 µmol/L and 108 µmol/L) attenuated high glucose-enhanced proliferation and migration of VSMCs. Exposure of VSMCs to the high glucose medium activated both the PKC-β2 and ERK1/2 MAPK, but not the p38 and JNK MAPK. Pretreatment with breviscapine (65 µmol/L and 108 µmol/L) blocked high glucose-induced increase of the ERK1/2 activity, but not that of the PKC-β2 activity. Conclusion: Our study demonstrated that breviscapine ameliorates high glucose-induced proliferation and migration of VSMCs via inhibiting ERK1/2 MAPK signaling.

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“…These protein kinases response against exogenous and endogenous stimuli by converting the sensing signal to a wide range of cellular responses, such as proliferation, survival, differentiation, and migration. Because of their essential roles in these cellular functions, perturbation in cascade activation of MAPKs may cause cancer development (Arnoldussen et al, 2009;Min et al, 2011). Hyperactivation of JNK has been recently shown to involve on human renal cell carcinomas (Liu et al, 2009).…”

Section: Discussionmentioning

confidence: 99%