[Effect of signal transduction inhibitors on human endometrial carcinoma cells with differential PTEN gene expression].
OBJECTIVE
To investigate the apoptotic and proliferation effects of signal transduction inhibitors on human endometrial carcinoma cells with different PTEN gene expression.


METHODS
PTEN antisense oligonucleotide and pcDNA3.1/PTEN vector contained PTEN gene were transfected into endometrial carcinoma cells (HEC-1A and Ishikawa). The expression of PTEN protein was detected by confocal spectral microscopy. The endometrial carcinoma cells (HEC-1A, HEC-1A-PTEN-null, Ishikawa, Ishikawa-PTEN) were treated with signal transduction inhibitors, RG-14620, SB203580 (SB) and rapamycin, respectively. Cell apoptosis morphology, cell apoptosis and cell cycle were detected by Hoechst 33258 staining and flow cytometry. Cell viability was determined by methyl thiazolyl tetrazolium assay.


RESULTS
The PTEN protein expression in two endometrial carcinoma cells (Ishikawa, HEC-1A) was exchanged by PTEN antisense oligonucleotide blocked and pcDNA3.1/PTEN stable transfected. After treated with RG-14620, SB and rapamycin, marked morphological changes of apoptosis were observed in HEC-1A-PTEN-null and Ishikawa cells. The cell apoptosis of HEC-1A-PTEN-null and Ishikawa cells exposed to SB were significantly increase [(31.6 +/- 0.8)% and (37.8 +/- 0.8)%, respectively], the G(1) phase cells were increased to (84.1 +/- 3.2)% and (87.5 +/- 1.9)%. While cell viability was significantly decreased in HEC-1A-PTEN-null and Ishikawa cells, the cell viability of HEC-1A-PTEN-null and Ishikawa cells exposed to SB were (54.0 +/- 2.1)% and (49.0 +/- 1.7)%.


CONCLUSIONS
Loss of PTEN in endometrial carcinoma cells may improve the G(1) phase cells and apoptotic effects, inhibit the cell proliferation, which due to the sensitivity of cells to related signal transduction inhibitors.
Xiao
Lan
L
Department of Gynecology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
Yang
Yue-bo
YB
Shen
Hui-min
HM
Xu
Cheng-fang
CF
Wang
Xiao-yun
XY
Li
Xiao-mao
XM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology; D014162:Transfection; D020032:Tyrphostins / Q000494:pharmacology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D020032:Tyrphostins; C070273:RG 14620; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C093642:SB 203580; D020123:Sirolimus