[Insulin/PI3K signalling pathway regulates the expression of survivin in liver cancer HepG2 cells].
OBJECTIVE
To determine the expression level changes of survivin, a inhibitor of apoptosis protein, followed by activation of insulin receptors in human hepatocellular carcinoma HepG2 cell line, and to investigate the signalling pathway involved in the regulation.


METHODS
Human hepatocellular carcinoma HepG2 cells were treated with insulin alone or pre-treated with LY294002, a specific inhibitor of PI3K signalling pathway, to determine whether blocking PI3K signaling can attenuate the up-regulation of survivin expression. Real time RT-PCR and Western blot analysis were used to measure survivin mRNA and protein changes before and after treatment, respectively.


RESULTS
Without serum supplement, HepG2 cells expressed a small amount of survivin. Insulin induced survivin expression in a dose- and time-dependent fashion. Survivin expression was blocked if cells were pre-treated with LY294002 prior to insulin stimulation.


CONCLUSIONS
Insulin induces survivin expression via PI3K signalling pathway, suggesting that to interfere the key gene in this signalling pathway may block survivin expression, therefore, promoting apoptosis in hepatocellular carcinoma cells.
Guo
Ren-hua
RH
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. guorenhua@csco.org.cn
Jin
Shi-dai
SD
Cai
Jie
J
Huang
Zu-hu
ZH
Shu
Yong-qian
YQ
D017209:Apoptosis; D002867:Chromones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D000077022:Survivin; D015854:Up-Regulation
C107489:BIRC5 protein, human; D002867:Chromones; D051034:Inhibitor of Apoptosis Proteins; D007328:Insulin; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D000077022:Survivin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one