Effect of human epidermal growth factor receptor 2 (HER2) downregulation on lapatinib/cisplatin resistance in lapatinib-resistant (LR) cell lines. SNU-216 LR3 and LR7 cells were infected with a lentivirus containing either control shRNA (shCtrl) or HER2 shRNA (shHER2). Cell viability was measured by crystal violet assay. (A) The protein expressions of HER2, pAKT, and AKT were determined by Western blot analysis. (B) Twenty-four hours after plating, cells were cultured for 3 days and cell growth was determined at the indicated times. (C) Cells were treated with the indicated concentrations of lapatinib, and cell viability was measured after 3 days. The percentage of viable cells is shown relative to untreated cells (considered as 100%). (D) Cells were treated with the indicated concentrations of cisplatin, and cell viability was measured after 3 days. The percentage of viable cells is shown relative to untreated cells (considered as 100%). (E) Cells were treated with the 1 μmol/L lapatinib alone or combined with 10 μg/mL cisplatin (CDDP), and cell viability was measured after 3 days. The percentage of viable cells is shown relative to untreated cells (considered as 100%). Each bar represents the mean±standard deviation. ns, not significant. a)p < 0.05 vs. shCtrl cells, b)p < 0.05 vs. lapatinib-treated shCtrl cells, c)p < 0.05 vs. cisplatin-treated shCtrl cells, d)p < 0.05 vs. shCtrl cells, e)p < 0.05 vs. lapatinib-treated shHER2 cells.