• 제목/요약/키워드: carcinoma, hepatocellular

검색결과 891건 처리시간 0.028초

Growth Inhibitory Activity of Honokiol through Cell-cycle Arrest, Apoptosis and Suppression of Akt/mTOR Signaling in Human Hepatocellular Carcinoma Cells

  • Hong, Ji-Young;Park, Hyen Joo;Bae, KiHwan;Kang, Sam Sik;Lee, Sang Kook
    • Natural Product Sciences
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    • 제19권2호
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    • pp.155-159
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    • 2013
  • Honokiol, a naturally occurring neolignan mainly found in Magnolia species, has exhibited a potential anti-proliferative activity in human cancer cells. However, the growth inhibitory activity against hepatocellular carcinoma cells and the underlying molecular mechanisms has been poorly determined. The present study was designed to examine the anti-proliferative effect of honokiol in SK-HEP-1 human hepatocellular cancer cells. Honokiol exerted anti-proliferative activity with cell-cycle arrest at the G0/G1 phase and sequential induction of apoptotic cell death. The cell-cycle arrest was well correlated with the down-regulation of checkpoint proteins including cyclin D1, cyclin A, cyclin E, CDK4, PCNA, retinoblastoma protein (Rb), and c-Myc. The increase of sub-G1 peak by the higher concentration of honokiol ($75{\mu}M$) was closely related to the induction of apoptosis, which was evidenced by decreased expression of Bcl-2, Bid, and caspase-9. Hohokiol was also found to attenuate the activation of signaling proteins in the Akt/mTOR and ERK pathways. These findings suggest that the anti-proliferative effect of honokiol was associated in part with the induction of cell-cycle arrest, apoptosis, and dow-nregulation of Akt/mTOR signaling pathways in human hepatocellular cancer cells.

3D CACT-assisted Radiofrequency Ablation Following Transarterial Chemoembolization for Hepatocellular Carcinoma: Early Experience

  • Jiao, De-Chao;Han, Xin-Wei;Wu, Gang;Ren, Jian-Zhuang
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권17호
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    • pp.7897-7903
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    • 2015
  • Background: To explored the value of 3D C-arm CT (CACT) guidance system in performing radiofrequency ablation (RFA) following transarterial chemoembolizationon (TACE) for hepatocellular carcinomas. Materials and Methods: RFA of hepatocellular carcinomas (HCC) were performed on 15 patients (21 lesions) with the assistance of CACT guidance system. Technical success, procedure time, complications and patient radiation exposure were investigated. The puncture performance level was evaluated on a five-point scale (5-1: excellent-poor). Complete ablation rate was evaluated after two months follow-up using enhanced CT scans. Results: The technical success rate of RFA procedure under CACT navigation system was 100 %. Mean total procedure time was $24.24{\pm}6.53min$, resulting in a mean effective exposure dose of $15.4{\pm}5.1mSv$. The mean puncture performance level rated for CACT guided RFA procedure was $4.87{\pm}0.35$. Complete ablation (CA) was achieved in 20 (95.2%) of the treated 21 tumors after the first RFA session. None of patients developed intra-procedural complications. Conclusions: 3D CACT guidance system enables reliable and efficient needle positioning by providing real-time intraoperative guidance for performing RFA on HCCs.

miR-340 Reverses Cisplatin Resistance of Hepatocellular Carcinoma Cell Lines by Targeting Nrf2-dependent Antioxidant Pathway

  • Shi, Liang;Chen, Zhan-Guo;Wu, Li-li;Zheng, Jian-Jian;Yang, Jian-Rong;Chen, Xiao-Fei;Chen, Zeng-Qiang;Liu, Cun-Li;Chi, Sheng-Ying;Zheng, Jia-Ying;Huang, Hai-Xia;Lin, Xiang-Yang;Zheng, Fang
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권23호
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    • pp.10439-10444
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    • 2015
  • Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR-340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.

MACC1 Expression Correlates with PFKFB2 and Survival in Hepatocellular Carcinoma

  • Ji, Dong;Lu, Zhong-Tang;Li, Yao-Qing;Liang, Zhe-Yong;Zhang, Peng-Fei;Li, Chao;Zhang, Jun-Li;Zheng, Xin;Yao, Ying-Min
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권2호
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    • pp.999-1003
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    • 2014
  • Objective: To validate the relationship between MACC1 and 6-phosphofructo-2-kinase/fructose 2, 6 bisphosphatase (PFKFB2) expression as well as its clinicopathological features and prognostic significance in hepatocellular carcinoma. Methods: By using immunohistochemistry, we investigated the MACC1 and PFKFB2 protein expression in 60 pairs of hepatocellular carcinoma and corresponding non-tumor tissues. Using the Mann-Whitney U test, the Chi-square test, Kaplan-Meier survival analysis, Cox proportional hazard regression analysis and Spearman analysis, we studied the relationship between MACC1 and PFKFB2 protein expression and postoperative overall survival (OS) of the HCC patients. Results: MACC1 and PFKFB2 positive staining rates were significantly higher in hepatocellular carcinoma than in the corresponding nontumor tissues (P=0.012 and 0.04, respectively). The clinicopathological features evaluation revealed that positive expression of MACC1 was associated with a high Edmondson classification (P=0.007) and advanced TNM stage (P=0.027). Similar findings were evident for PFKFB2 expression (P=0.002 and P=0.027). MACC1 and PFKFB2 positive expression was associated with a lower OS rate (P=0.004 and 0.03, respectively). Kaplan-Meier survival and Cox proportional hazard regression analyses revealed MACC1 positive expression to be a prognostic factor for postoperative OS, but PFKFB was not. Conclusion: Highly expressed MACC1 and PFKFB2 protein were associated with TNM stage, Edmondson-Steier classification and overall survival. MACC1 may affect tumor metabolism partly through expression and phophorylation of PFKFB2.

Increased Serum Endoglin and Transforming Growth Factor β1 mRNA Expression and Risk of Hepatocellular Carcinoma in Cirrhotic Egyptian Patients

  • Teama, Salwa;Fawzy, Amal;Teama, Shirin;Helal, Amany;Drwish, Amira Diyaa;Elbaz, Tamer;Desouky, Eman
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권5호
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    • pp.2429-2434
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    • 2016
  • Transforming growth factor-B1 ($TGF-{\beta}1$ )and its coreceptor endoglin (ENG) have been shown to contribute to hepatocellular tumor development and malignant progression. Our aim was to evaluate the serum expression levels of $ENG/TGF-{\beta}1$ mRNAs and risk of hepatocellular carcinoma in cirrhotic Egyptian patients. Our study included 77 subjects. Real time polymerase chain reaction was used to evaluate the expression level of ENG and $TGF-{\beta}1$mRNAs. The relative expression ratio of ENG mRNA was 0.82 (0.1 -3.2), 0.66 (0.15-5.3), 0.38(0.007-2.8) and 0.12 (0.00-0.22) and the relative expression ratio of $TGF-{\beta}1$mRNA was 1.4 (0.19 -6.2), 1.2 (0.22-4.3), 1.0 (0.15-4.4) and 0.6 (0.00-2.2) for cirrhotic HCC cirrhotic, HCC only and healthy control groups respectively. Increased ENG and $TGF-{\beta}1$ mRNA gene expression was correlated with TNM clinical stage. The expression ratio in TNM stage III-IV 1.1 (0.07-3.2), 1.55 (0.15-6.2) was statistically significantly higher than that in stage I-II 0.47 (0.007-2.8), 1.0 (0.31-4.4) (P<0.05). Our data suggested that increased ENG and $TGF-{\beta}1$ gene expression may participate in hepatocarcinogenesis and increased risk of HCC in individuals with cirrhosis. Early screening for evidence of cirrhosis and consideration of ENG and $TGF-{\beta}1$ as targets for therapy and treatment strategies are warranted.

지방간에 대한 백두구 에틸아세테이트 추출물의 억제 효과 및 기전 연구 (Study of the Suppressive Effect and Its Mechanism of Amomum Cardamomum L. on Free Fatty Acid-induced Liver Steatosis)

  • 임동우;김혁;박성윤;박선동;박원환;김재은
    • 동의생리병리학회지
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    • 제31권3호
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    • pp.159-166
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    • 2017
  • Through this study, the authors investigated the anti-steatosis effects of the Amomum cardamomum ethyl acetate fraction in free fatty acids (FFAs)-induced human hepatocellular carcinoma HepG2 cells. The ethyl acetate fraction of Amomum cardamomum (ACEA) was extracted with 70% ethanol and then the extract was evaporated using a rotary evaporator prior to sequential fractionation. Human hepatocellular carcinoma were treated with different concentrations of ACEA in the presence and absence of FFAs. To demonstrate the reactive oxygen species (ROS) scavenging activity, DCFDA level was analyzed by using in vitro assay system. Cell viability, lipid accumulation, intracellular triglycerides, malondialdehyde (MDA), liver steatosis related signaling molecules and inflammatory cytokines such as interleukin (IL)-6, 8, tumor necrosis factor-alpha ($TNF-{\alpha}$) were also investigated. As results, ACEA inhibited the FFAs-induced ROS, lipid accumulation, intracellular triglycerides, and MDA in a dose dependent manner. Treatment of human hepatocellular cells with ACEA induced the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) and carnitine palmitoyltransferase I (CPT1) expression using western blot analysis. ACEA also potently suppressed the FFAs-induced inflammatory cytokines including IL-6, IL-8 and $TNF-{\alpha}$. These results suggest that the ethyl acetate fraction of Amomum cardamoum extract own inhibitory effects of liver steatosis by inhibiting ROS, lipid accumulation, intracellular triglycerides, MDA through AMPK signaling and anti-inflammatory actions.