Enhanced blocking with PI3K-β and PI3K-δ inhibitors in ibrutinib-resistant DLBCL cells. (A) Knockdown of PI3K-β expression was performed in ibrutinib-resistant DLBCL cell lines by stable expression of PI3K-β isoform–specific short hairpin RNA as described in “Materials and methods.” Expression analyses of PI3K isoforms demonstrate the success of PI3K-β knockdown in ibrutinib-resistant DLBCL cell lines. (Please note that the expression of PI3K isoform shown here is for ibrutinib-resistant cells and not the parental cell line.) (B) Western blots representing pAKT levels and activity of mTOR substrate in PI3K-β knockdown ibrutinib-resistant DLBCL cells after idelalisib treatment. (C) Viability of cells treated with idelalisib after PI3K-β isoform knockdown of ibrutinib-resistant DLBCL cells was analyzed using an MTT cell proliferation assay. (D) Drug dose matrix data of ibrutinib-resistant DLBCL cells. The numbers in the matrix indicate the percentage of growth inhibition of cells treated with inhibitors (AZD6482 and idelalisib) either as single agents or in combination, relative to cells treated with control vehicle. Data were visualized over the matrix using a color scale. Unpaired Student t test was used for statistical analysis.