[Effects of SODD and survivin on leukemia cell apoptosis induced by chemotherapeutic drugs].
This study was aimed to investigate the changes of silencer of death domains (SODD), survivin, caspase 3, caspase 8 and caspase 9 in the apoptotic process of human leukemia cells induced by chemotherapeutic drugs in order to explore the molecular mechanism of apoptotic modulatory genes and to search for the new target of chemotherapeutic drugs. After Jurkat cells were induced by chemotherapeutic drugs, the translocated phosphatidylserine was labeled with annexin V/PI, and the apoptosis incidence was measured by FCM; The expression changes of SODD, caspase 3, caspase 8 and caspase 9 were determined by Western blot; the changes of survivin mRNA and protein were determined by RT-PCR and immunohistochemistry SABC method respectively. The results indicated that high expressions of SODD and survivin could inhibit apoptotic signaling pathway; VCR down-regulated the function of SODD protein and effectively induced the apoptosis of Jurkat cells in a time-dependent manner and activates caspase 3 through the death receptor-mediated activation of caspase 8, in which caspase 9 and survivin were not degraded. It is concluded that SODD participates in the apoptotic process induced by VCR which induces the Jurkat cell apoptosis by downregulating expression of SODD protein and priming death receptor pathway. In the apoptotic process, the mitochondrion apoptotic pathway is not trigged.
Tao
Hong-Fang
HF
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Hu
Qun
Q
Fang
Jian-Lin
JL
Liu
Ai-Guo
AG
Liu
Shuang-You
SY
Zhang
Liu-Qing
LQ
Hu
Ying
Y
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019169:Jurkat Cells; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D000077022:Survivin; D014750:Vincristine / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C116906:BAG4 protein, human; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D014750:Vincristine; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9