Tamoxifen-induced apoptosis of rat C6 glioma cells via PI3K/Akt, JNK and ERK activation.
To elucidate the mechanism of TAM treatment on gliomas, we hypothesised that PI3K/Akt and MAPK signaling pathway may play important roles on TAM-induced apoptosis in C6 glioma cells. Our results demonstrated that TAM induced apoptosis of C6 glioma cells in a dose-dependent manner. The activation of AKT significantly decreased in a time-dependent manner in response to TAM treatment, JNK was transiently activated, and subsequently decreased activation and kept stable level, whereas ERK evidenced sustained activations in response to the drug treatment. The inhibition of PI3K/Akt and JNK both accelerated and enhanced TAM-induced apoptosis and ERK inhibition apparently exerted negative effect on apoptosis. We also observed that PI3K/Akt had intimate association with JNK and ERK activation in TAM-induced apoptosis. These findings may provide strategies for the molecularly targeted therapy in malignant gliomas.
Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province 510080, PR China.
Ying
Y
Feng
Jintao
J
Huang
Ying
Y
Ding
Fukang
F
Xie
Xiaoyan
X
Shen
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism / Q000502:physiology*; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D058990:Molecular Targeted Therapy; D051058:Oncogene Protein v-akt / Q000378:metabolism / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases