Chemotherapeutic Agents Augment TRAIL-Induced Apoptosis in Human Hepatocellular Carcinoma Cell Lines
| Autor: | Takeshi Nakano, Takenari Yamanaka, Katsuya Shiraki, Takeshi Ito, Masami Moriyama, Katsuhiko Fujikawa, Masaaki Ito, Koujiro Takase, Atsushi Suzuki, Kazushi Sugimoto |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Carcinoma Hepatocellular medicine.medical_treatment Antineoplastic Agents Apoptosis Biology Receptors Tumor Necrosis Factor TNF-Related Apoptosis-Inducing Ligand Internal medicine Tumor Cells Cultured medicine Humans Doxorubicin Decoy receptors Cytotoxicity Receptor Antibiotics Antineoplastic Membrane Glycoproteins Hepatology Tumor Necrosis Factor-alpha Liver Neoplasms NF-kappa B Endocrinology Cytokine Cell culture Dactinomycin Cancer research Camptothecin Apoptosis Regulatory Proteins medicine.drug |
| Zdroj: | Hepatology. 32:482-490 |
| ISSN: | 1527-3350 0270-9139 |
| Popis: | TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in various transformed cell lines but not in almost-normal tissues. It is regulated by 2 death receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2, and 2 decoy receptors, TRAIL-R3 and TRAIL-R4. We investigated the expression of TRAIL-R– and TRAIL-induced apoptosis in human hepatocellular carcinomas (HCCs). TRAIL-R1, -R2, and -R4 were expressed in 6 HCC cell lines examined, but TRAIL-R3 was expressed in only 2 of the 6 cell lines. In addition, immunohistochemical results revealed a high and prevalent expression of TRAIL-R1 and -R2 in human HCC tissues. Despite the expression of TRAIL-R1 and -R2, all 6 HCC cell lines showed resistance to TRAIL-induced apoptosis with no relation to nuclear factor κ B (NF-κB) levels induced by TRAIL. TRAIL-induced death signal was inhibited with both decreased caspase-8 and caspase-3 activity. However, TRAIL induced significant apoptosis in the presence of a subtoxic level of actinomycin D, indicating that the TRAIL-induced apoptotic pathway is in place in these cell lines. In addition, we found that treatment with conventional chemotherapeutic agents, doxorubicin and camptothecin, dramatically augmented TRAIL-induced cytotoxicity in most of the HCC cell lines. Actinomycin D and camptothecin almost completely suppressed NF-κB induction by TRAIL, whereas doxorubicin had little effect. These results indicate that TRAIL, in combination with chemotherapeutic agents, may have therapeutic potential in the treatment of human HCC. (Hepatology 2000;32:482-490.) |
| Databáze: | OpenAIRE |
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