Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells

Baradari, Viola; Höpfner, Michael; Huether, Alexander; Schuppan, Detlef; Scherübl, Hans

doi:10.3748/wjg.v13.i33.4458

Cited by 52 publications

(40 citation statements)

References 51 publications

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“…The IC 50 of EGI-1 cells to gemcitabine was 0.051 AE 0.012 mmol/L and that of TFK-1 to gemcitabine was 0.45 AE 0.35 mmol/L, which is consistent with previous reports for these cells (21)(22)(23). Two combination protocols were evaluated in cell culture: sequential treatment consisting of 24-hour exposure to 1 mmol/L AZD6244 followed by incubation in drug-free medium for 24 hours, then 24-hour treatment with 0 to 10 mmol/L gemcitabine, or simultaneous exposure to 1 mmol/L AZD6244 and gemcitabine for 24 hours.…”

Section: Cell-cycle Effects Of Azd6244 and Their Relation To Gemcitabsupporting

confidence: 82%

Sequence Dependence of MEK Inhibitor AZD6244 Combined with Gemcitabine for the Treatment of Biliary Cancer

Knox

Ibrahimov

et al. 2013

Clinical Cancer Research

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Purpose: MEK inhibition has clinical activity against biliary cancers and might therefore be successfully combined with gemcitabine, one of the most active chemotherapy agents for these cancers. As gemcitabine is active in S-phase, and the extracellular signal-regulated kinase (ERK) pathway has a major role driving cellcycle progression, concurrent use of a MEK inhibitor could potentially antagonize the effect of gemcitabine. We therefore tested the sequence dependence of the combination of gemcitabine and the MEK inhibitor AZD6244 using a series of biliary cancer models.Experimental Design: Primary xenografts were established from patients with gallbladder and distal bile duct cancer and grown in severe combined immunodeficient (SCID) mice at the subcutaneous site. Plasma and tumor drug levels and the time course for recovery of ERK signaling and S-phase were measured in tumor-bearing mice treated for 48 hours with AZD6244 and then monitored for 48 hours off treatment. On the basis of these results, two different treatment schedules combining AZD6244 with gemcitabine were tested in four different biliary cancer models.Results: DNA synthesis was suppressed during treatment with AZD6244, and reentry into S-phase was delayed by approximately 48 hours after treatment. Strong schedule dependence was seen in all four biliary cancer models tested, suggesting that combined treatment with AZD6244 plus gemcitabine would be more active in patients with biliary cancer when gemcitabine is given following a 48-hour interruption in AZD6244 dosing, rather than concurrently.Conclusions: The combination of AZD6244 plus gemcitabine is highly schedule dependent, and predicted to be more effective in the clinic using sequential rather than simultaneous dosing protocols.

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Section: Cell-cycle Effects Of Azd6244 and Their Relation To Gemcitabsupporting

confidence: 82%

Sequence Dependence of MEK Inhibitor AZD6244 Combined with Gemcitabine for the Treatment of Biliary Cancer

Knox

Ibrahimov

et al. 2013

Clinical Cancer Research

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“…This is most likely due to apoptosis resistance of CC cells and subsequently weak efficacy of common chemotherapeutical regimes. The induction of apoptosis in human CC cells is barely observed [25,27] or only detectable after co-treatment of the cells with additional drugs or inhibiting RNAs [28][29][30]. Accordingly, the understanding and the therapy of CC are characterized by nescience and ineffectiveness.…”

Section: Discussionmentioning

confidence: 99%

Impact of Salinomycin on human cholangiocarcinoma: induction of apoptosis and impairment of tumor cell proliferation in vitro

Lieke¹,

Ramackers²,

Bergmann³

et al. 2013

Z Gastroenterol

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Background: Cholangiocarcinoma (CC) is a primary liver cancer with increasing incidence worldwide. Despite all efforts made in past years, prognosis remains to be poor. At least in part, this might be explained by a pronounced resistance of CC cells to undergo apoptosis. Thus, new therapeutic strategies are imperatively required. In this study we investigated the effect of Salinomycin, a polyether ionophore antibiotic, on CC cells as an appropriate agent to treat CC. Salinomycin was quite recently identified to induce apoptosis in cancer stem cells and to overcome apoptosis-resistance in several leukemia-cells and other cancer cell lines of different origin. Methods: To delineate the effects of Salinomycin on CC, we established an in vitro cell culture model using three different human CC cell lines. After treatment apoptosis as well as migration and proliferation behavior was assessed and additional cell cycle analyses were performed by flowcytometry.

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“…Our results show that TSA could shorten the survival time of gallbladder carcinoma and cholangiocarcinoma cell lines in vivo and in vitro, indicating that TSA is a potential drug for the treatment of biliary tract cancer. It was reported that HDACIs MS-275, NVP-LBH589 and NVP-LAQ824 can effectively inhibit the growth of human biliary tract cancer cells [26,27] . However, early diagnosis and treatment of biliary tract cancer are still difficult [29][30][31][32][33][34] .…”

Section: Discussionmentioning

confidence: 99%

Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines

Xu¹,

Wang²,

Zou³

2008

WJG

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AIM:To explore the effect of histone deacetylase inhibitor, trichostatin A (TSA) on the growth of biliary tract cancer cell lines (gallbladder carcinoma cell line and cholangiocarcinoma cell line) in vivo and in vitro , and to investigate the perspective of histone deacetylase inhibitor in its clinical application. METHODS:The survival rates of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) treated with various doses of TSA were detected by methylthiazol tetrazolium (MTT) assay. A nude mouse model of transplanted gallbladder carcinoma (Mz-ChA-l cell line) was successfully established, and changes in the growth of transplanted tumor after treated with TSA were measured. RESULTS:TSA could inhibit the proliferation of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) in a dose-dependent manner. After the nude mouse model of transplanted gallbladder carcinoma (MzChA-l cell line) was successfully established, the growth of cancer was inhibited in the model after treated with TSA. C O N C L U S I O N :T S A c a n i n h i b i t t h e g r o w t h o f cholangiocarcinoma and gallbladder carcinoma cell lines in vitro and in vivo.

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Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells

Cited by 52 publications

References 51 publications

Sequence Dependence of MEK Inhibitor AZD6244 Combined with Gemcitabine for the Treatment of Biliary Cancer

Sequence Dependence of MEK Inhibitor AZD6244 Combined with Gemcitabine for the Treatment of Biliary Cancer

Impact of Salinomycin on human cholangiocarcinoma: induction of apoptosis and impairment of tumor cell proliferation in vitro

Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines

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