[Effects of a JAK inhibitor, AG490, on proliferation and survivin expression of breast cancer cell line MDA-MB-231].
OBJECTIVE
Many researches have proven that Survivin is expressed abundantly and is involved in tumorigenesis and prognosis of breast cancers. However, the signal transduction pathway of Survivin in breast cancer cells is still not clear. This study was to investigate the effects of AG490, a JAK enzyme inhibitor, on the expression of Survivin and on the proliferation and apoptosis of human breast cancer cell line MDA-MB-231.


METHODS
MDA-MB-231 cells were treated with AG490. The protein levels of P-STAT3 and Survivin were detected by Western blot; the mRNA level of survivin was measured by reverse transcription-polymerase chain reaction (RT-PCR). Cell proliferation was detected by MTT; cell apoptosis was detected by flow cytometry (FCM).


RESULTS
AG490 reduced the expression of P-STAT3 and Survivin, inhibited cell proliferation and induced apoptosis in MDA-MB-231 cells. When treated with 40 micromol/L AG490 for 24 h, the protein level of P-STAT3 was decreased from 0.74 to 0.21, and that of Survivin was decreased from 1.09 to 0.28. The "sub-G1" peak appeared and the apoptosis rate was 5.62% at 24 h, and further reached 28.81% at 48 h.


CONCLUSIONS
AG490 could induce apoptosis and reduce the expression of Survivin in breast cancer MDA-MB-231 cells.
Yu
Chang
C
Department of Pathophysiology, Chongqing University of Medical Sciences, Chongqing, 400016, P. R. China. cqdenghy@yahoo.com.cn.
Deng
Hua-Yu
HY
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; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000077022:Survivin; D020032:Tyrphostins / Q000494:pharmacology*
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D053612:Janus Kinases