Cytotoxic effects of camptothecin and cisplatin combined with tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) in a model of primary culture of non-small cell lung cancer.
BACKGROUND
The cytokine tumor-necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) has been shown to preferentially induce apoptosis in cancer cells. A previous study of our group demonstrated that non-small cell lung cancer cell lines can be sensitized to Apo2L/TRAIL-induced apoptosis by chemotherapeutic agents. The aim of the present study was the evaluation of these results in a model of primary culture of non-small cell lung cancer.


METHODS
Lung cancer tissue and normal lung tissue obtained from 8 patients who underwent operation were cultured and treated with Apo2L/TRAIL alone and in combination with cisplatin and the topoisomerase I inhibitor camptothecin for different periods. Metabolic activity of the tissue was measured by alamar blue. Markers for apoptosis were determined by immunohistochemistry and Western blot. Expression of Apo2L/TRAIL receptors in primary lung cancer and normal lung tissue was evaluated by semi-quantitative RT-PCR. Statistics were performed using nonparametric repeated measures Anova with Dunnett's correction.


RESULTS
Treatment with cisplatin, camptothecin and the combination of camptothecin and Apo2L/TRAIL demonstrated significant reduction of metabolic activity in tumor and normal lung tissue. In addition, the combination of camptothecin plus Apo2L/TRAIL revealed greater cytotoxic activity in cancer tissue compared with normal lung tissue. Importantly, no toxic activity of Apo2L/TRAIL alone in normal lung tissue was observed.


CONCLUSIONS
Our results obtained in a model of primary culture of lung cancer suggest that the combination of Apo2L/TRAIL and camptothecin might present an effective strategy for the treatment of non-small cell lung cancer.
Frese
Steffen
S
Laboratory of Thoracic Surgery, University Hospital Bern, Murtenstrasse 35 room C807, CH-3010 Berne, Switzerland. steffen.frese@dkf.unibe.ch
Schüller
Alexandra
A
Frese-Schaper
Manuela
M
Gugger
Mathias
M
Schmid
Ralph A
RA
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage*
D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D002945:Cisplatin; D002166:Camptothecin