Fig. 5
Analysis of the mechanisms for reversal of P-gp or BCRP mediated MDR ability in the MDR cancer cells with P110α or P110β knocked out. a Immunofluorescence microscopic characterization of down-regulation of P-gp or BCRP expression in KB-C2 and H460/MX80 cells with target P110α and P110β subunits knocked out. PI3K 110α and 110 β subunit-k.o. KB-C2 (namely KB-C2-k.o.110α and KB-C2-k.o.110β, respectively) cells expressing low level of P-gp or BCRP were depicted by arrows in orange, as most cells of these two populations were hardly be detected with positive signals, as confirmed by IF-Cytell statistical analysis according to description in the methods. The cells were seeded to 96-well plate at a density of 5 × 103 cells per well. This experiment was independently repeated at least three times. b Western blot for the analysis of P-gp and BCRP expression in KB-C2 and H460/MX80 cells with target P110 subunits knocked out. c Relative protein expression level was calculated according to the band showing protein density and volume. d and e MTT assay showing poor effect of GSK-2110183 to reverse P-gp- or BCRP-mediated drug-resistance in KB-C2 or H460/MX20. f GSK-2110183 reduces cell viability via lower their ability to proliferate or anti-apoptosis. KB-3-1, H460, KB-C2 and H460/MX20 cells were cultured with gradient concentrations of GSK-2110183