LY294002 induces p53-dependent apoptosis of SGC7901 gastric cancer cells.
OBJECTIVE
To study the effects of LY294002, an inhibitor of class I phosphatidylinositol 3-kinase (PI3K), on proliferation and apoptosis of SGC7901 gastric cancer cells.


METHODS
The MTT assay was used to determine the cytotoxic effects of LY294002. Cell cycle distribution was analyzed using flow cytometry and apoptosis was assessed using flow cytometry analysis after staining DNA with propidium iodide. Mitochondrial membrane potential was measured using the fluorescent probe JC-1. Expression of p53 and PUMA was determined using real-time RT-PCR and Western blotting analysis.


RESULTS
The viability of SGC7901 cells was significantly reduced by LY294002 treatment. Expression of p53 and PUMA was induced, and mitochondrial membrane potential collapsed after treatment with LY294002. LY294002 induced apoptotic cell death.


CONCLUSIONS
Activation of the p53 pathway is involved in LY294002-induced SGC7901 cell death.
Xing
Chun-gen
CG
Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou 215004, China.
Zhu
Bao-song
BS
Liu
Hui-hui
HH
Lin
Fang
F
Yao
Hui-hua
HH
Liang
Zhong-qin
ZQ
Qin
Zheng-hong
ZH
D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000378:metabolism; D002232:Carbocyanines / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000378:metabolism; D005562:Formazans / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D001562:Benzimidazoles; D002232:Carbocyanines; D002867:Chromones; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D005562:Formazans; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013778:Tetrazolium Salts; D016159:Tumor Suppressor Protein p53; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; C079782:MTT formazan; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one