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Enhancement of Apo2L/TRAIL (tumor necrosis factor–related apoptosis-inducing ligand)–induced apoptosis in non–small cell lung cancer cell lines by chemotherapeutic agents without correlation to the expression level of cellular protease caspase-8 inhibitory protein

Enhancement of Apo2L/TRAIL (tumor necrosis factor–related apoptosis-inducing ligand)–induced apoptosis in non–small cell lung cancer cell lines by chemotherapeutic agents without correlation to the expression level of cellular protease caspase-8 inhibitory protein

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FRESE, Steffen, Thomas BRUNNER, Mathias GUGGER, Aima UDUEHI, Ralph A. SCHMID, 2002. Enhancement of Apo2L/TRAIL (tumor necrosis factor–related apoptosis-inducing ligand)–induced apoptosis in non–small cell lung cancer cell lines by chemotherapeutic agents without correlation to the expression level of cellular protease caspase-8 inhibitory protein. In: The Journal of Thoracic and Cardiovascular Surgery. 123(1), pp. 168-174. ISSN 0022-5223. Available under: doi: 10.1067/mtc.2002.119694

@article{Frese2002Enhan-14293, title={Enhancement of Apo2L/TRAIL (tumor necrosis factor–related apoptosis-inducing ligand)–induced apoptosis in non–small cell lung cancer cell lines by chemotherapeutic agents without correlation to the expression level of cellular protease caspase-8 inhibitory protein}, year={2002}, doi={10.1067/mtc.2002.119694}, number={1}, volume={123}, issn={0022-5223}, journal={The Journal of Thoracic and Cardiovascular Surgery}, pages={168--174}, author={Frese, Steffen and Brunner, Thomas and Gugger, Mathias and Uduehi, Aima and Schmid, Ralph A.} }

First publ. in: Journal of Thoracic and Cardiovascular Surgery ; 123 (2002), 1. - S. 168-174 Brunner, Thomas Brunner, Thomas 2002 eng Objective:<br />Apo2L/tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a potential anticancer drug that promotes apoptosis specifically in tumor cells. Because not all cancer cells are susceptible to Apo2L/TRAIL, the aim of our study was to determine whether non–small cell lung cancer cells can be sensitized by chemotherapeutic agents for Apo2L/TRAIL-induced apoptosis. In addition, endogenous expression levels of the caspase-inhibiting cellular protease caspase-8 inhibitory protein (C-FLIP) were measured to investigate partial resistance to Apo2L/TRAIL.<br />Methods:<br />Six human lung cancer cell lines (A549, NCI-H358, Calu1, Calu6, SkMes1, and SkLu1) were incubated with soluble Apo2L/TRAIL and two different concentrations each of cisplatin, paclitaxel, doxorubicin, 5-fluorouracil, and camptothecin. After 24 hours the rate of apoptosis was measured by annexin V/propidium iodide staining followed by FACScan analysis. Expression levels of C-FLIP in cell lines and lung cancer biopsy specimens were determined by Western blotting.<br />Results:<br />Treatment of lung cancer cells with Apo2L/TRAIL alone resulted in apoptotic cell death in four cell lines (P < .001). Combining Apo2L/TRAIL and chemotherapeutic agents enhanced the rate of apoptosis significantly. Statistical analysis revealed a synergistic effect of Apo2L/TRAIL in combination with 1.8 mmol/L camptothecin and 100 μmol/L cisplatin, each in four of the six cell lines (P < .002). Western blot analysis showed that sensitization to Apo2L/TRAIL did not correlate with the expression of cellular protease caspase-8 inhibitory protein. Furthermore, no increased cellular protease caspase-8 inhibitory protein levels relative to those in normal lung tissue could be found in non–small cell lung cancer specimens from 12 patients. Conclusion: Apo2L/TRAIL-induced apoptosis in non–small cell lung cancer cell lines is significantly enhanced by chemotherapeutic agents. Resistance and sensitization to Apo2L/TRAIL are not correlated with the endogenous expression level of cellular protease caspase-8 inhibitory protein, implying that in non–small cell lung cancer other mechanisms are responsible for inhibition of the Apo2L/TRAIL pathway. Even though the molecular mechanism remains unclear, the combination of Apo2L/TRAIL with chemotherapy may be a promising treatment modality for non–small cell lung cancer. Gugger, Mathias Schmid, Ralph A. Enhancement of Apo2L/TRAIL (tumor necrosis factor–related apoptosis-inducing ligand)–induced apoptosis in non–small cell lung cancer cell lines by chemotherapeutic agents without correlation to the expression level of cellular protease caspase-8 inhibitory protein Uduehi, Aima Schmid, Ralph A. Frese, Steffen 2011-10-21T11:56:22Z Uduehi, Aima Gugger, Mathias deposit-license 2011-10-21T11:56:22Z Frese, Steffen

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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