Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer

Lemstrova, Radmila; Melichar, Bohuslav; Mohelníková-Duchoňová, Beatrice

doi:10.1007/s00280-016-3058-y

Cited by 30 publications

(24 citation statements)

References 71 publications

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“…Single-agent gemcitabine therapy is still an acceptable treatment in patients with advanced disease and reduced performance status, as well as in the adjuvant setting after surgical resection (12). Nab-paclitaxel (Abraxane ® ; Celgene Inc., Odenton, MD, USA) is a specific formulation of paclitaxel that was developed to improve its solubility and to overcome resistance due to the desmoplastic stroma surrounding PDAC cells (13). Paclitaxel is a taxane and acts by reversibly binding to tubulin, causing defects in mitotic functions that lead to blockage of the cell cycle and eventually to apoptosis, with mechanisms that differ from those of gemcitabine.…”

Section: Co-treatment With Gemcitabine and Nab-paclitaxel Exerts Addimentioning

confidence: 99%

Co-treatment with gemcitabine and nab-paclitaxel exerts additive effects on pancreatic cancer cell death

Passacantilli

Panzeri²,

Terracciano³

et al. 2018

Oncol Rep

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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer and current treatments exert small effects on life expectancy. The most common adjuvant treatment for PDAC is gemcitabine. However, relapse almost invariably occurs and most patients develop metastatic, incurable disease. The aim of the present study was to assess the activity of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) alone or in combination with gemcitabine in PDAC cell lines displaying different degrees of sensitivity to gemcitabine treatment. We evaluated the effects of gemcitabine and nab-paclitaxel and their combination on cell proliferation, death, apoptosis and cell cycle distribution in PDAC cell lines either sensitive to gemcitabine, or with primary or secondary resistance to gemcitabine. Our results indicated that the dose‑response of PDAC cell lines to nab-paclitaxel was similar, regardless of their sensitivity to gemcitabine. In addition, nab-paclitaxel elicited similar cytotoxic effects on a PDAC cell line highly resistant to gemcitabine that was selected after prolonged exposure to the drug. Notably, we found that combined treatment with gemcitabine and nab-paclitaxel exerted additive effects on cell death, even at lower doses of the drugs. The combined treatment caused an increase in cell death by apoptosis and in cell cycle blockage in S phase, as assessed by flow cytometry and western blot analysis of the PARP-1 cleavage. These results revealed that a combined treatment with nab-paclitaxel may overcome resistance to gemcitabine and may represent a valuable therapeutic approach for PDAC.

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Section: Co-treatment With Gemcitabine and Nab-paclitaxel Exerts Addimentioning

confidence: 99%

Co-treatment with gemcitabine and nab-paclitaxel exerts additive effects on pancreatic cancer cell death

Passacantilli

Panzeri²,

Terracciano³

et al. 2018

Oncol Rep

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“…As per as anticancer activity is concerned, PT, exclusively bind to the β-tubulin subunit through N-terminal side chain with 31 amino acid, in the microtubules 4, 5 causing depolymerization of β-tubulin subunit, with inhibition of mitosis and these combined effect can be directed to induction of cell apoptosis 6 . Based on previous reports, PT shows anticancer activities towards breast cancer 7 , ovarian cancer 8 , lung cancer 9 and pancreatic cancer 10 . Supportive to this, previous published reports by Mullins et al,11 , shows that PT gives antitumor activity by formation of macrophage IL -12 through nitric oxide, which further caused to dysregulation of IL-12 p40 expression and finally reduces the tumour growth.…”

Section: Introductionmentioning

confidence: 80%

Untitled

2017

IJPSR

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ABSTRACT:The present study was assessed to determine the effect of various grades of phospholipids on liposomes. The various grades of synthetic phospholipids such as Phospholipon 90G ® (PL90G), Phospholipon 80H ® (PL80H) and Phospholipon 90H ® (PL90H) were used along with cholesterol in stoichiometric ratio (1:0.25, 1:0.5, 1:1, 1:2, 1:3). Using these ratios the paclitaxel liposome was formulated by film hydration method. The prepared liposomes were assessed for characterization using entrapment efficiency, vesicular size, in vitro release and hemolytic toxicity assay. The synthetic grades of phospholipids significantly influenced paclitaxel liposomal formulations. The stoichiometric ratio (1:1) between cholesterol and various synthetic phospholipids was found to be optimized one, from rest of ratios. The characterization confirmed the formation of liposomes. The entrapment efficiency was observed to be high as increasing the ratios between cholesterol and phospholipids, but then declined suddenly as further increasing the ratio. The best liposomal formulations showed the spherical shape with size ranging from <10µm. The optimized paclitaxel liposomes % release in phosphate buffer (pH 7.4) enhanced significantly, and rest of ratios. The optimized liposomal formulation also lowers the hemolytic toxicity of paclitaxel.

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“…Metastasis is another critical factor associated with the poor OS in PC patients. Therefore, investigators have tried new combination drug therapy regimens in order to prolong OS of metastatic PC patients (5,6,25,26). We conducted wound healing assay to evaluate migration ability of PC cells in the presence of baicalein at different concentrations or in combination treatment.…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of baicalein with gemcitabine or docetaxel on the proliferation, migration and apoptosis of pancreatic cancer cells

Liu

Feng

Sun

et al. 2017

International Journal of Oncology

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Baicalein, a type of flavonoids extracted from Scutellaria baicalensis Georgi, has been reported to be a very promising drug for pancreatic cancer. However, it is unclear whether combination of baicalein with gemcitabine or docetaxel is synergistic to the treatment for pancreatic cancer (PC). We investigated the combinational effects of baicalein with gemcitabine or docetaxel on proliferation, cell cycle, migration and apoptosis of human PC cells. Administration of baicalein alone significantly inhibit the proliferation of PC cells. Notably, when it is combined with gemcitabine or docetaxel, combination index (CI) values calculated by Calcusyn software are smaller than 1, indicating the synergism of baicalein with gemcitabine or docetaxel for the treatment of PC cells. Consistently, EdU assay showed that administration of baicalein significantly enhanced the capacity of gemicitabine to inhibit proliferation of PC cells. Cell cycle analysis showed that high-concentration of baicalein was able to arrest PC cells in the S phase. Furthermore, low concentration of baicalein in combination with either gemcitabine or docetaxel exhibited strong suppression on the migration of PC cells. A further study using transmission electron microscope (TEM), DAPI staining and western blot showed that baicalein induced-apoptosis of PC cells might be via caspase-3/PARP signaling pathway. Notably, combination treatment was able to induce more severe cell apoptosis of PC cells. In conclusion, baicalein exhibited synergistic effects with gemcitabine or docetaxel on the treatment of PC cells.

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Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer

Cited by 30 publications

References 71 publications

Co-treatment with gemcitabine and nab-paclitaxel exerts additive effects on pancreatic cancer cell death

Co-treatment with gemcitabine and nab-paclitaxel exerts additive effects on pancreatic cancer cell death

Untitled

Synergistic effects of baicalein with gemcitabine or docetaxel on the proliferation, migration and apoptosis of pancreatic cancer cells

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