Docetaxel inhibits progression of human hepatoma cell line <i>in vitro</i> and is effective in advanced hepatocellular carcinoma

Yata, Yutaka; Xue, Feng; Takahara, Taro; Kudo, Hiroshi; Hirano, Katsuharu; Yasumura, Satoshi; Minemura, Masami; Scanga, Andrew; Sugiyama, Toshiro

doi:10.1111/j.1872-034x.2009.00598.x

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…Docetaxel was revealed to inhibit the growth of hepatoma cells by arresting the G2/M-phase, activating caspases, and fragmenting DNA (32). A recent investigation confirmed that docetaxel inhibited the progression of cultured human hepatoma cells in advanced HCC (33). In the present study, we also revealed that docetaxel inhibited proliferation while promoting apoptosis in CD133-expressing HCC stem cells through the inactivation of the PI3K/AKT signaling pathway.…”

Section: Discussionsupporting

confidence: 76%

Docetaxel promotes cell apoptosis and decreases SOX2 expression in CD133‑expressing hepatocellular carcinoma stem cells by suppressing the PI3K/AKT signaling pathway

Shao

Cui

et al. 2018

Oncol Rep

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Docetaxel is a front-line standard-of-care chemotherapeutic drug for the treatment of cancers. However, the underlying function and mechanism of docetaxel in human hepatocellular carcinoma (HCC) are uncertain. Therefore, the present study aimed to determine the effects of docetaxel on cell apoptosis and SOX2 expression in cultured human HCC stem cells. After human HCC stem cells were treated with docetaxel, cell proliferation was assessed by methyl thiazolyl tetrazolium (MTT) method, the cell apoptotic rate was evaluated by flow cytometry, the expression of CD133 and sex determining region Y-box 2 (SOX2) was determined by RT-PCR and immunohistochemistry, and the protein levels of CD133, SOX2, phosphoinositide 3-kinases (PI3K), AKT and phosphorylated AKT (p-AKT) were analyzed by western blotting. The results indicated that SOX2 and CD133 were highly expressed in patients with HCC while their expression was significantly decreased after patients with HCC were treated with docetaxel. In vitro, docetaxel inhibited the proliferation while it enhanced the apoptosis of human CD133-expressing HCC stem cells. Furthermore, lower expression of p-AKT and SOX2 were revealed in the presence of docetaxel. Notably, docetaxel-inhibited SOX2 expression and growth of human CD133-expressing HCC stem cells were partially restricted following the block of the PI3K/AKT signaling pathway using the inhibitor LY294002. The present study collectively indicated that docetaxel promoted apoptosis and upregulated SOX2 expression of human HCC stem cells through the suppression of the PI3K/AKT signaling pathway.

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Section: Discussionsupporting

confidence: 76%

Docetaxel promotes cell apoptosis and decreases SOX2 expression in CD133‑expressing hepatocellular carcinoma stem cells by suppressing the PI3K/AKT signaling pathway

Shao

Cui

et al. 2018

Oncol Rep

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“…2A). OOS was also evaluated in combination with other drugs that had exhibited efficacy in the treatment of patients with HCC, including the antitumoral agents cisplatin (24) and docetaxel (25,26). However, treatment with OOS in combination with these agents did not substantially improve the effect of the individual treatments (Fig.…”

Section: Resultsmentioning

confidence: 99%

Antitumoral effect of Ocoxin in hepatocellular carcinoma

et al. 2017

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Hepatocellular carcinoma (HCC) is becoming one of the most prevalent types of cancer worldwide. The most efficient types of treatment at present include surgical resection and liver transplantation, but these treatments may only be used in a small percentage of patients. In order to identify novel therapeutic strategies for this disease, the present study explored the potential antitumoral effect of Ocoxin® oral solution (OOS) in HCC. OOS inhibited the proliferation of HCC cell lines in a time- and dose-dependent manner, being more efficient when used in combination with sorafenib, a standard of care treatment for patients diagnosed with advanced-stage disease. Mechanistic studies indicated that the effect of OOS was due to the induction of cell cycle arrest rather than the stimulation of apoptotic cell death. The cell cycle was slowed down in all phases in the HCC cell lines treated with OOS. Finally, when tested in animal models of HCC, OOS reduced tumor progression through the induction of necrosis in xenograft tumor models. Considering the poor prognosis and high resistance to antitumor treatments of HCC, the antiproliferative action of OOS, particularly in combination with sorafenib, provides the opportunity to investigate the effect of combined therapy in a clinical setting.

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“…There has no agreement concerning the most valuable drugs to administer by HAIC, and their optimal condi-tions including dose and therapeutic period. As for the usefulness of chemotherapies, to assess the sensitivity of anti-cancer drugs against individual cancer cells is very important to obtain excellent long-term survival [32]. Three-day FPL seems to advantageous regimen to discern the sensitivity and effectiveness with shorter duration.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of 5-Fluorouracil and High-Concentration Cisplatin Suspended in Lipiodol by Short-Term Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

Yata¹,

Namikawa²,

Ohyama³

et al. 2015

JCT

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Background: Since advanced hepatocellular carcinoma (HCC) is potentially fatal, and patients' quality of life (QOL) often deteriorates during their treatment, improving the prognosis and QOL of patients given chemotherapy is very important. In addition, cost-effective treatments are highly desirable when chemotherapy must be given repeatedly. The aim of this study was to evaluate the efficacy and usefulness of 5-fluorouracil (5-FU) and high-concentration cisplatin by short-term hepatic arterial infusion chemotherapy (3-day FPL) in advanced HCC patients. Methods: Thirty patients with unresectable advanced HCC were enrolled. The patients underwent hepatic arterial infusion chemotherapy via the implanted port system with 5-FU on days 1 -3 and a fine-powder formulation of cisplatin in suspended pre-warmed lipiodol on day 2 every 4 to 10 weeks. Tumor response was assessed one month later with CT. Results: All patients had evidence of portal vein invasion (Vp2-4). Four patients achieved a complete response (CR), 8 patients achieved a partial response (PR), and 7 patients had stable disease (SD). The median progression-free survival (PFS) and overall survival (OS) were 198 days and 452 days, respectively. The OS was significantly long-* Corresponding author.Y. Yata et al. 1152 er in the successful disease control group (CR, PR, and SD) than in the progressive disease group (P < 0.005). Conclusions: Three-day FPL was effective and tolerable in advanced HCC patients due to its shorter time of administration than conventional FP therapy. Therefore, repetitive 3-day FPL appears useful and contributes to improving the prognosis and QOL of patients with advanced HCC. In addition, this protocol is a cost-effective treatment.

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Docetaxel inhibits progression of human hepatoma cell line in vitro and is effective in advanced hepatocellular carcinoma

Abstract: In this study, we present a therapeutic approach by using DTX that supports the potential usefulness of personalized medicine in vitro and demonstrates it clinically.

Cited by 7 publications

References 18 publications

Docetaxel promotes cell apoptosis and decreases SOX2 expression in CD133‑expressing hepatocellular carcinoma stem cells by suppressing the PI3K/AKT signaling pathway

Docetaxel promotes cell apoptosis and decreases SOX2 expression in CD133‑expressing hepatocellular carcinoma stem cells by suppressing the PI3K/AKT signaling pathway

Antitumoral effect of Ocoxin in hepatocellular carcinoma

Efficacy of 5-Fluorouracil and High-Concentration Cisplatin Suspended in Lipiodol by Short-Term Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

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