[Effect and mechanism of LY294002 on growth of fibrosarcoma cell line HT1080].
OBJECTIVE
To investigate the effect and mechanism of LY294002 on growth of fibrosarcoma cell line HT1080.


METHODS
The proliferation inhibitory rate of HT1080 cells treated by LY294002 at doses of 5, 10, 25, 50, 100 micromol/L for 12 and 24 h, respectively, was evaluated using SunBio Am-Blue method. HT1080 cells were divided into two groups, that is, A and B. The A group was control group without treatment. The B group received LY294002 (100 micromol/L) for 24 h. The changes of cell morphology and quantity were observed by phase contrast microscope. The apoptosis rate of HT1080 cells was detected by flow cytometry. And the protein expression of p-Akt and p-mTOR in HT1080 cells were detected by Western Blotting.


RESULTS
The proliferation of HT1080 cells was inhibited in time- and dose- dependent manner by LY294002. After the treatment of 100 micromol/L LY294002 for 24 h, the growth of HT1080 cell line was remarkably inhibited by LY294002. The rate of apoptosis increased. And the protein expression of p-Akt (0.23 +/- 0.01) and p-mTOR (0.32 +/- 0.06) in LY294002 group was lower than p-Akt (0.63 +/- 0.02) and p-mTOR (0.71 +/- 0.02) in control group (P<0. 01).


CONCLUSIONS
LY294002 can inhibit the growth of HT1080 cells through PI3K-mTOR pathway. PI3K-mTOR pathway presents an appealing therapeutic target on fibrosarcoma.
Zhou
Hong
H
Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Huang
Xiang-Yang
XY
Yang
Ting
T
Wang
Tao
T
Xu
Dan
D
Wen
Fu-Qiang
FQ
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000473:pathology*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D002867:Chromones; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases