Significance of COX-2 and C/EBP β expression in hepatocellular carcinoma

Liu, Xi; Hu, Yanan; He, Shuixiang; Deng, Yuan; Li, Xiaofeng; Zhang, Yaxin; Hou, Helei; Zhu, Zhanfang

doi:10.11569/wcjd.v18.i28.3040

Cited by 2 publications

(5 citation statements)

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“…Building on our previous work, which identified the significant role of SSd in COX2 suppression in hepatocarcinogenesis and its chemo-preventative effects in HCC (He et al, 2006; He et al, 2014; Liang et al, 2010; Lu et al, 2012), in this report, we extended our study to show that anti-tumorigenic effects of SSd act through the intermediatory p-STAT3/C/EBPβ signaling pathway to suppress COX-2. SSd effectively inhibited cell proliferation in a dose-dependent manner via regulating apoptosis.…”

Section: Discussionsupporting

confidence: 62%

“…Furthermore, anti-inflammatory drugs, such as salicylate, suppressed COX-2 expression via inhibition of C/EBPβ binding to the COX-2 promoter (Cieslik et al, 2002). Our previous study demonstrated a correlation between C/EBPβ overexpression and COX-2 overexpression in human HCC tissue (Liang et al, 2010). Collectively, these studies provide further support for our present findings, which show that activation of the C/EBPβ and COX-2 pathway plays a vital role in carcinogenesis.…”

Section: Discussionmentioning

confidence: 85%

“…Our laboratory has played an important role in describing the significance of SSd suppression of COX-2 in HCCs and the SSd’s chemo-preventive effect on liver cancer associated with COX-2 inhibition (He et al, 2006;He et al, 2014; Liang et al, 2010; Lu et al, 2012). In this study, we extended these findings to understand the upstream mechanism of COX-2 inhibition by SSd treatment.…”

Section: Introductionmentioning

confidence: 99%

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Saikosaponin-d Suppresses COX2 Through p-STAT3/C/EBPβ Signaling Pathway in Liver Cancer: A Novel Mechanism of Action

Ren

McGowan

et al. 2019

Front. Pharmacol.

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Saikosaponin-d (SSd) is an active extract from Radix Bupleuri , the dried root from the plant Bupleurum falcatum used in China for thousands of years to treat liver diseases. The SSd extract possesses valuable pharmacological activities including anti-cancer and anti-inflammatory effects; however, the mechanism underlying the anti-cancer activity of SSd is largely unknown. Here, we explored the mechanism of action of SSd as an anti-cancer agent for liver cancer in two human hepatocellular carcinoma cell lines. Using MTT and annexin-V-FITC/PI assays, Western blots, immunohistochemistry, qRT-PCR, luciferase reporter assay, and a JAK2-specific inhibitor (AG490), we demonstrated that the anti-tumorigenic effects of SSd act through the intermediatory p-STAT3/C/EBPβ signaling pathway to suppress cyclooxygenase (COX)-2. SSd effectively inhibited cell proliferation in a dose-dependent manner. Apoptosis was significantly increased in cells treated with SSd (2.5–15 µg/ml) with concurrent increase and decrease in pro- and anti-apoptosis proteins, respectively. COX-2, C/EBPβ, and p-STAT3 were significantly decreased, at both the translational and transcriptional levels, by SSd treatment. AG490 produced similar inhibitory effects on STAT3, p-STAT3, C/EBPβ, and COX-2. In conclusion, our data suggest that SSd controls liver cancer proliferation through suppression of the p-STAT3/C/EBPβ signaling pathway inhibiting COX2 expression. These findings further our understanding of the pharmacological action of SSd, providing new information on SSd mechanism of action and showing potential for SSd as a novel therapy for liver cancer.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Saikosaponin-d Suppresses COX2 Through p-STAT3/C/EBPβ Signaling Pathway in Liver Cancer: A Novel Mechanism of Action

Ren

McGowan

et al. 2019

Front. Pharmacol.

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“…Moreover, SSD has been reported to attenuate toxin-induced hepatocyte injury and hepatic fibrosis in animal models though the inhibition of several types of inflammatory mediators (32,33). Our previous studies revealed that C/EBPβ and COX-2 were overexpressed in human HCC tissues and a positive correlation was found (34). We also found that SSD inhibited lipopolysaccharideinduced COX-2 expression in the HCC SMMC-7721 cell line in vitro (35).…”

Section: Introductionmentioning

confidence: 80%

“…In human prostate tissues, the expression of C/EBPβ and COX-2 was highly correlated and was involved in chronic inflammation and prostate cancer development (45). Our previous study demonstrated that C/ EBPβ overexpression was correlated with COX-2 overexpression in human HCC tissue (34). All of these investigations provide evidences for our present finding that C/EBPβ and COX-2 are relatedly overexpressed in rat liver tumors induced by DEN, although double immunostaining to define the precise co-expression was not carried out.…”

Section: Discussionmentioning

confidence: 97%

Chemopreventive effect of saikosaponin-d on diethylinitrosamine-induced hepatocarcinogenesis: Involvement of CCAAT/enhancer binding proteinï¿½β and cyclooxygenase-2

Ren

et al. 2011

Mol Med Report

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Abstract. Cyclooxygenase-2 (COX-2) and CCAAT/enhancer binding protein β (C/EBPβ) have been shown to be involved in inflammation and carcinogenesis, and our previous study revealed that they were co-overexpressed in human hepatocellular carcinoma (HCC) tissue and a positive correlation was found. Saikosaponin-d (SSD), a triterpene saponin extracted from Bupleurum falcatum L. (Umbelliferae), is known to exert inhibitory effects on COX-2 expression, together with inflammation and hepatic fibrosis. These findings prompted us to investigate the chemopreventive potential of SSD against hepatocarcinogenesis and its possible molecular mechanism in vivo. An experimental model with diethylinitrosamine (DEN)-treated Sprague Dawley rats was used in the present study. DEN (50 mg/kg body weight) and SSD (2 mg/kg body weight) were intraperitoneally injected weekly and daily, respectively. Administration of SSD alone had no side effects. The liver nodule formation, tumorous invasion to surrounding organs and increased cellular atypia induced by DEN were markedly reduced by SSD in the SSD + DEN group compared with the DEN group. On the other hand, immunohistochemical staining demonstrated that the expression of COX-2 and C/ EBPβ proteins was significantly increased in tumor cells and macrophages of liver tissue from DEN-treated rats, whereas the expression of the two proteins was markedly lowered in the SSD + DEN group. Overall, our results suggest that SSD prevents DEN-induced hepatocarcinogenesis in rats through inhibition of C/EBPβ and COX-2, providing indispensable experimental evidence for the clinical application of SSD as a novel chemopreventive agent against HCC in the future.

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Significance of COX-2 and C/EBP β expression in hepatocellular carcinoma

Cited by 2 publications

References 0 publications

Saikosaponin-d Suppresses COX2 Through p-STAT3/C/EBPβ Signaling Pathway in Liver Cancer: A Novel Mechanism of Action

Saikosaponin-d Suppresses COX2 Through p-STAT3/C/EBPβ Signaling Pathway in Liver Cancer: A Novel Mechanism of Action

Chemopreventive effect of saikosaponin-d on diethylinitrosamine-induced hepatocarcinogenesis: Involvement of CCAAT/enhancer binding proteinï¿½β and cyclooxygenase-2

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