[Death mode of Hep-3B and A549 tumor cells induced by bluetongue virus strain HbC3].
OBJECTIVE
To study the death mode of human hepatocellular carcinoma Hep-3B cells and human lung adenocarcinoma A549 cells induced by bluetongue virus strain HbC3 (BTV-HbC3) and the mechanism of its action.


METHODS
BTV-HbC3 was used to infect the tumor cells, and the cytopathic effects (CPE) was observed. TUNEL staining was used to detect the apoptosis of tumor cells induced by BTV-HbC3. The changes of endoplasmic reticulum and nuclei treated with BTV-HbC3 were further examined by laser scanning confocal microscopy. The activities of caspase-3/7, caspase-8 and caspase-9 were determined by fluorescence analysis.


RESULTS
Hep-3B cells were sensitive to BTV-HbC3. Lots of early apoptotic cells were found by TUNEL staining. The laser scanning confocal microscopic examination showed characteristics of apoptosis, such as pyknotic nuclei, margination of nuclear chromatin and vacuolization of endoplasmic reticulumin in Hep-3B cells exposed to BTV-HbC3. The activity of caspase-3/7 was increased, but the activity changes of caspase-8 and caspase-9 were not found. A549 cells were sensitive to BTV-HbC3 too. But no apoptotic cells were observed by TUNEL staining. The results of laser scanning confocal microscopy showed marked vacuolization of endoplasmic reticulum, but chromatin margination was not found after A549 cells was exposed to BTV-HbC3. The activity of caspase-3/7 and caspase-9 was increased, but the activity of caspase-8 was not changed.


CONCLUSIONS
BTV-HbC3 induces apoptosis of Hep-3B tumor cells mainly through endoplasmic reticulum signal transduction pathway, and the features of cell death in A549 cells could be described as paraptosis.
Chen
Jie
J
State Key Laboratory of Virology, Wuhan University School of Medicine, China.
Hu
Jun
J
Dong
Chang-yuan
CY
Liang
Ke
K
Dai
Ying
Y
Gao
Jing
J
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000821:virology; D017209:Apoptosis; D001820:Bluetongue virus / Q000472:pathogenicity* / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000821:virology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D050504:Oncolytic Viruses / Q000472:pathogenicity* / Q000502:physiology; D015398:Signal Transduction
D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9