Skip to main content
. 2022 Nov 1;128(1):148–159. doi: 10.1038/s41416-022-02032-w

Fig. 5. Activation of the PI3K pathway confers resistance to sotorasib.

Fig. 5

a, b MTT assay showed that a combination treatment of alpelisib and sotorasib had a greater cytotoxic effect than sotorasib treatment alone on MIA PaCa-2 cells and LU65 cells. c, d Similar synergistic cytotoxic effects were observed in the combination treatment of copanlisib and sotorasib in MIA PaCa-2 cells. e Results of western blotting confirmed the efficacy of shRNA-mediated PTEN knockdown in MIA PaCa-2 cells. f Results of western blotting demonstrated the enhancement of AKT phosphorylation by the constitutively active mutants PIK3CA-E545K and PIK3CA-H1047R and the knockdown of PTEN in MIA PaCa-2 cells. g Overexpression of constitutively active mutants PIK3CA-E545K and PIK3CA-H1047R in MIA PaCa-2 cells resulted in resistance to sotorasib treatment. h PTEN knockdown significantly reduced the sensitivity of MIA PaCa-2 cells to sotorasib treatment. i, j Analysis of genetic changes occurring in pulmonary adenocarcinoma and colorectal cancer using The Cancer Genome Atlas PanCancer Atlas data revealed that KRAS mutations are nearly mutually exclusive with PIK3CA-activating or PTEN loss-of-function mutations in pulmonary adenocarcinoma; of a total of 217 colorectal cancers with KRAS mutation, 92 (42.4%) had PIK3CA-activating or PTEN loss-of-function mutations. #CI < 1 at the indicated dose (n = 6 for a–d, g, h).