Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is being evaluated clinically for cancer therapy, selectively induces apoptosis in tumor cell lines without causing toxicity to normal cells. However, its therapeutic potential is limited by occurring resistance in a majority of lung carcinoma, breast and prostate cells. Various chemotherapeutic drugs have been found to enhance TRAIL-induced apoptosis. The objective of this study was to examine whether non-small cell lung cancer (NSCLC) cell line A-549, one of the most drug-resistant tumor cells in human, can be sensitized by doxorubicin (DOX) to TRAIL-mediated apoptosis. We show that DOX and recombinant human TRAIL (TRAIL) have a synergistic cytotoxic effect against A-549 cells in vitro. However, no obvious antitumor effects were observed in A-549 tumor bearing nude mice treated by TRAIL alone, DOX alone or both agents, suggesting that further works should be carried to improve the efficacy of combined treatment of DOX and TRAIL.
Keywords: Apoptosis, A-549 cell lines, Combined treatment, Doxorubicin, Non-Small Cell Lung Cancer, TRAIL, DU-145 cell lines, DOX, NSCLC, therapeutic plateau, angiogenesis, necrosis, tumor, caspases
Letters in Drug Design & Discovery
Title: Doxorubicin Sensitizes the Non-Small Cell Lung Cancer Cells to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Mediated (TRAIL) Apoptosis In Vitro but not In Vivo
Volume: 8 Issue: 9
Author(s): Li Fan, Liangran Guo, Jinfeng Ren, Yulong Ren, Zhiqing Pang and Xinguo Jiang
Affiliation:
Keywords: Apoptosis, A-549 cell lines, Combined treatment, Doxorubicin, Non-Small Cell Lung Cancer, TRAIL, DU-145 cell lines, DOX, NSCLC, therapeutic plateau, angiogenesis, necrosis, tumor, caspases
Abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is being evaluated clinically for cancer therapy, selectively induces apoptosis in tumor cell lines without causing toxicity to normal cells. However, its therapeutic potential is limited by occurring resistance in a majority of lung carcinoma, breast and prostate cells. Various chemotherapeutic drugs have been found to enhance TRAIL-induced apoptosis. The objective of this study was to examine whether non-small cell lung cancer (NSCLC) cell line A-549, one of the most drug-resistant tumor cells in human, can be sensitized by doxorubicin (DOX) to TRAIL-mediated apoptosis. We show that DOX and recombinant human TRAIL (TRAIL) have a synergistic cytotoxic effect against A-549 cells in vitro. However, no obvious antitumor effects were observed in A-549 tumor bearing nude mice treated by TRAIL alone, DOX alone or both agents, suggesting that further works should be carried to improve the efficacy of combined treatment of DOX and TRAIL.
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Fan Li, Guo Liangran, Ren Jinfeng, Ren Yulong, Pang Zhiqing and Jiang Xinguo, Doxorubicin Sensitizes the Non-Small Cell Lung Cancer Cells to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Mediated (TRAIL) Apoptosis In Vitro but not In Vivo, Letters in Drug Design & Discovery 2011; 8 (9) . https://dx.doi.org/10.2174/157018011797200867
DOI https://dx.doi.org/10.2174/157018011797200867 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
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