Fig. 4

Pharmacological inhibition of PI3K, MAPK and SRC signaling pathways re-sensitizes resistant GC cells to lapatinib. OE19 cells transduced with CSK targeting sgRNAs or PTEN targeting sgRNAs were used for following test. OE19 cells transduced with non-targeting sgRNA as control. a Growth curve of test groups with 0.05 μM lapatinib in combination with indicated dose of trastuzumab for 6 days. b Growth curve of test groups treated with indicated dose of SRC inhibitor AZD0530 for 6 days. c Growth curve of test group treated with 0.05 μM lapatinib in combination with indicated dose of PI3K inhibitor copanlisib for 6 days. d Growth curve of test groups treated with 0.05 μM lapatinib in combination with different doses of mTOR inhibitor rapamycin for 6 days. e Growth curve of test groups treated with 0.05 μM lapatinib in combination with different doses of MEK inhibitor trametinib for 6 days. f Inhibition effect of 0.05 μM lapatinib alone or in combination with 0.1 μM trametinib or /and 0.1 μM copanlisib for 6 days. Unpaired Student’s t test indicated the following: *significant difference from the control, p < 0.05; **significant difference from the control, p < 0.01