[Apoptosis resistance induced by leptin and its mechanism in breast cancer cells].
OBJECTIVE
To explore the apoptosis resistance induced by Leptin and its mechanism in breast cancer cells in vitro.


METHODS
The leptin-mediated reduction of docetaxel-induced apoptosis in human breast cancer T47D cells was evaluated by TransAM ELISA, MTT and caspase-9 assay. The leptin-promoted survivin expression was analyzed by Western-blot and RT-PCR. The reversing effect of STAT3 knockdown on leptin-induced survivin upregulation was measured by Western-blot and RT-PCR.


RESULTS
Leptin promoted T47D cells proliferation and the inhibitory rate was -63.6%. It reduced docetaxel-induced apoptosis in T47D cells by 31.9%. Leptin at different concentrations promoted survivin protein and mRNA expression in T47D cells. The expression of survivin mRNA was 4.6 fold compared with the T47D cells not treated with leptin(10 nmol/L). The expression of survivin mRNA in T47D cells was 0.55 +/- 0.15 fold after transfected with small interfering RNA (siRNA) of STAT3. The expression of survivin mRNA in STAT3 siRNA group and mock transfected group were 0.56 +/- 0.18 fold and 1.61 +/- 0.22 fold after treated by leptin, respectively. The survivin protein level of T47D mock transfected cells was increased after treated by leptin, but the protein level of T47D transfected with STAT3 siRNA cells were not changed significantly.


CONCLUSIONS
Leptin/STAT3 signaling is a novel pathway for up-regulation of survivin expression in breast cancer cells.
Zhao
Tian-suo
TS
Department of Pancreatic Oncology, Cancer Institute and Hospital of Tianjin Medical University, Tianjin, China.
Jiang
Hai-ping
HP
Wang
Xiu-chao
XC
Ren
He
H
Hao
Ji-hui
JH
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D020738:Leptin / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000077022:Survivin; D014162:Transfection; D015854:Up-Regulation
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D020738:Leptin; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin