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Synergistic anti-tumor efficacy of doxorubicin and flavopiridol in an in vivo hepatocellular carcinoma model.

Published on Nov 1, 2015in Journal of Cancer Research and Clinical Oncology3.332
· DOI :10.1007/s00432-015-1990-6
Min Sun Kwak13
Estimated H-index: 13
(SNU: Seoul National University),
Su Jong Yu22
Estimated H-index: 22
(SNU: Seoul National University)
+ 6 AuthorsChung Yong Kim31
Estimated H-index: 31
(SNU: Seoul National University)
Abstract
Purpose A previous study showed that flavopiridol increased doxorubicin sensitivity in hypoxic hepatocellular carcinoma (HCC) cells by increasing apoptosis through suppressing hypoxia-inducible N-myc downstream-regulated gene-1 (NDRG1) expression. However, this has not been investigated in an in vivo HCC model. Therefore, we aimed to elucidate whether the combination of doxorubicin and flavopiridol has a synergistic anti-tumor effect in an in vivo HCC model.
  • References (29)
  • Citations (8)
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References29
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#1Qingfeng Xiang (SYSU: Sun Yat-sen University)H-Index: 5
#2Dong-Mei Zhang (JNU: Jinan University)H-Index: 24
Last. Changzhen Shang (SYSU: Sun Yat-sen University)H-Index: 8
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Background & Aims: Cabozantinib, a small-molecule multitargeted tyrosine kinase inhibitor, has entered into a phase III clinical trial for the treatment of hepatocellular carcinoma (HCC). This study assessed the mechanistic effect of cabozantinib on the reversal of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR). Methods: CCK-8 assays and tumour xenografts were used to investigate the reversal of MDR in vitro and in vivo respectively. Substrate retention assays were evaluated by fluore...
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#2Bing Song (Anhui Medical University)H-Index: 3
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Background Endoplasmic reticulum stress (ER stress) is generally activated in solid tumors and results in tumor cell anti-apoptosis and drug resistance. Paeonol (Pae, 2-hydroxy-4-methoxyacetophenone), is a natural product extracted from the root of Paeonia Suffruticosa Andrew. Although Pae displays anti-neoplastic activity and increases the efficacy of chemotherapeutic drugs in various cell lines and in animal models, studies related to the effect of Pae on ER stress–induced resistance to chemot...
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#1Jun Zhou (Fudan University)H-Index: 5
#2Bo Wan (Fudan University)H-Index: 20
Last. Long Yu (Fudan University)H-Index: 37
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Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The mechanisms by which hepatoma cells resist apoptosis induced by doxorubicin are largely unknown. MAPKAPK5 (MK5), also named as p38-regulated/activated protein kinase (PRAK), has been identified as a crucial mediator of skin tumorigenesis in mouse and colon cancerogenesis in human. Here, we describe a novel role of MK5 in doxorubicin-induced apoptosis in human hepatoma cells. Expression of MK5 was hig...
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ObjectiveTumor recurrence and metastasis is the most common cause of mortality in hepatocellular carcinoma (HCC) patients. Despite positive results with vascular endothelial growth factor (VEGF) inhibitors in preclinical studies using HCC xenograft models, the clinical outcome in HCC patients has be
12 CitationsSource
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Hepatocellular carcinoma (HCC) is the fifth most common cancer and it is the third leading cause of cancer- related deaths worldwide. Once diagnosed with the disease, only 30-40% of patients are deemed eligible for curative intention with treatment modalities including surgical resection, liver transplantation, and chemoembolization. Eventually, most patients will receive some forms of chemotherapy in hope of prolonging life. Sorafenib is the first molecular inhibitor to be approved by the FDA f...
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Abstract Hypoxia may activate survival signals in cancer cells. Moreover, hypoxic cells are less sensitive than normoxic cells to doxorubicin cytotoxicity, a potent activator of the p53 tumor suppressor gene. N-myc downstream-regulated gene-1 (NDRG1) is a hypoxia- and retinoic acid-inducible protein, and has been previously implicated in carcinogenesis. As this protein is also a downstream target of p53 and hepatocellular carcinoma (HCC) cells frequently evidence resistance to retinoic acid (RA)...
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#2Xianghu Qu (VUMC: Vanderbilt University Medical Center)H-Index: 4
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