Chemotherapeutic Agents Augment TRAIL-Induced Apoptosis in Human Hepatocellular Carcinoma Cell Lines

• DOI: 10.1053/jhep.2000.16266
• Publication Date: 2004-03-19T22:04:05Z
• Authors: Takenari Yamanaka; Katsuya Shiraki; Kazushi Sugimoto; Takeshi Ito; Katsuhiko Fujikawa; Masaaki Ito; Koujiro Takase; Masami Moriyama; Takeshi Nakano; Atsushi Suzuki
• Keywords: Camptothecin

TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in various transformed cell lines but not almost-normal tissues. It is regulated by 2 death receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2, decoy TRAIL-R3 TRAIL-R4. We investigated the expression of TRAIL-R– TRAIL-induced human hepatocellular carcinomas (HCCs). TRAIL-R1, -R2, -R4 were expressed 6 HCC examined, was only lines. In addition, immunohistochemical results revealed a high prevalent TRAIL-R1 -R2 Despite all showed resistance to with no relation nuclear factor κ B (NF-κB) levels induced TRAIL. signal inhibited both decreased caspase-8 caspase-3 activity. However, significant presence subtoxic level actinomycin D, indicating that apoptotic pathway place these we found treatment conventional chemotherapeutic agents, doxorubicin camptothecin, dramatically augmented cytotoxicity most Actinomycin D camptothecin almost completely suppressed NF-κB induction TRAIL, whereas had little effect. These indicate combination may have therapeutic potential HCC.