Protein kinase B inhibitor enhance sensitivity of gastric cancer cell to etoposide / 中华胃肠外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>