The growth inhibition of liver cancer cells by paclitaxel and the involvement of extracellular signal-regulated kinase and apoptosis.
Paclitaxel is a chemotherapeutic drug applied for the treatment of breast and non-small cell lung cancers. However, the biological effects of paclitaxel on hepatocellular carcinoma (HCC) are undefined. We examined these points by using the human HCC cell lines, and found that paclitaxel inhibited the growth of HCC cells and blocked the cell cycle at the G2/M phase. The cell death was partially mediated by apoptosis, because caspases were weakly activated and the cell death was partially rescued by a pan-caspase inhibitor. Paclitaxel activated extracellular signal-regulated kinase (ERK), and when ERK was inhibited by a mitogen-activated ERK-regulating kinase inhibitor, the cell death and cell cycle arrest induced by paclitaxel were rescued, demonstrating that paclitaxel inhibited the cellular growth via the ERK signaling pathway. Our data are promising for the application of paclitaxel in the treatment of patients with HCC.
Okano
Jun-Ichi
J
Second Department of Internal Medicine, Tottori University School of Medicine, Tottori 683-8504, Japan. okanoj@hotmail.co.jp
Nagahara
Takakazu
T
Matsumoto
Kazuya
K
Murawaki
Yoshikazu
Y
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D053144:Cell Nucleus Shape / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D053453:Caspase 9; D017239:Paclitaxel