[Effect of signal transduction inhibitors on human endometrial carcinoma cells with differential PTEN gene expression].

Abstract

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)%.

CONCLUSION:

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.

• Authors: Lan Xiao, Yue-bo Yang, Hui-min Shen, Cheng-fang Xu, Xiao-yun Wang, Xiao-mao Li
• Journal: Zhonghua fu chan ke za zhi (Zhonghua Fu Chan Ke Za Zhi) Vol. 44 Issue 9 Pg. 681-5 (Sep 2009) ISSN: 0529-567X [Print] China
• PMID: 20079181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Imidazoles
• Pyridines
• Tyrphostins
• RG 14620
• ErbB Receptors
• PTEN Phosphohydrolase
• PTEN protein, human
• SB 203580
• Sirolimus

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival
• Endometrial Neoplasms (metabolism, pathology)
• Enzyme Inhibitors (pharmacology)
• ErbB Receptors (antagonists & inhibitors, metabolism)
• Female
• Humans
• Imidazoles (pharmacology)
• PTEN Phosphohydrolase (genetics, metabolism)
• Pyridines (pharmacology)
• Signal Transduction (drug effects)
• Sirolimus (pharmacology)
• Transfection
• Tyrphostins (pharmacology)