[Protein kinase B inhibitor enhance sensitivity of gastric cancer cell to etoposide].
OBJECTIVE
To observe the effects of etoposide on protein kinase B (PKB) activity in distinct differentiated gastric cancer cell lines and the change of sensitivity to etoposide after pretreatment by wortmannin, a PKB inhibitor. To explore the relationship between PKB activity in gastric cancer cells and their sensitivity to etoposide chemotherapy.


METHODS
Four distinct differentiated gastric cancer cell lines, including MKN-28 (well differentiated), SGC-7901 (moderate differentiated), BGC-823 (poorly differentiated) and HGC-27 (undifferentiated), were studied. The PKB activities of these cell lines were detected by nonradioactive protein-kinase assay at different time points after etoposide treatment for 0,3,6,12,24 h with or without wortmannin pretreatment. Cell viabilities were assayed by MTT and cell apoptosis was analyzed by flow cytometry.


RESULTS
Poorer differentiated gastric cancer cell lines had higher PKB activities. Etoposide treatment resulted in increase in PKB activity and apoptosis rate,and decrease in cell survival rate in a time-dependent manner in gastric cancer cell lines. Wortmannin pretreatment abolished PKB activity completely in gastric cancer cells,and decreased survival rate and increased apoptosis rate in SGC-7901, BGC-823, and HGC-27 cell lines.


CONCLUSIONS
Etoposide can induce the PKB activity in gastric cancer cell lines. Wortmannin pretreatment enhances sensitivity of median and low differentiated gastric cancer cells to etoposide chemotherapy.
Xu
Xi-Ming
XM
Center of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, China. gewei514@126.com
Yu
Hong-Gang
HG
Wu
Yao-Gui
YG
Ge
Wei
W
D017209:Apoptosis; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D013274:Stomach Neoplasms / Q000188:drug therapy
D047428:Protein Kinase Inhibitors; D005047:Etoposide; D051057:Proto-Oncogene Proteins c-akt