Fig 2: Schematic diagram of the mechanism of p38 regulating ABCG2-mediated decrease in chemotherapeutic sensitivity

Fig 3: Inhibition of p38 reduces the efflux of tumor cells to multiple chemotherapeutic drugsSiHa cells were treated with MIT (A), TP (B), and DOX (C) after 1h of use of anisomycin or BIRB 796. The drug fluorescence accumulation was detected by flow cytometry. APC-A, PE-A, and FITC-A represented MIT, DOX, and TP respectively. n = 3 for each group. The relative accumulation of drugs is shown in Figure (D–F). After shCON or shp38 treatment, (G and H) the expression of p38 and p-p38 proteins and (I and J) the efflux of MIT, TP, and DOX in SiHa cells were measured. n = 3 for each group. Data are mean ± SD, ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.005.

Fig 4: p38 regulates the expression of ABCG2 oligomers on the cell membrane(A) The membrane protein of MCF7 cells was extracted to determine the expression of oligomerized ABCG2 affected by BIRB 796 or anisomycin. The quantitative results are shown in panel (B and C). n = 3 for each group.(D) Relative expression of membrane oligomerized ABCG2 in SiHa cells treated with BIRB 796 or anisomycin. n = 3 for each group.(E and F) The membrane protein was extracted to determine the expression of oligomerized ABCG2 affected by BIRB 796 or anisomycin. n = 3 for each group. Data are mean ± SD, ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.005.

Fig 5: p38 regulates the oligomeric formation of ABCG2(A and B) The protein expression of ABCG2 in SiHa cells treated with shCON or shp38. n = 3 for each group.(C–F) The protein levels of p-p38, p-38, ABCG2 monomer, and ABCG2 oligomer in SiHa cells and MCF7/ADR cells treated with different concentrations of BIRB 796 or anisomycin. n = 3 for each group.(G) A schematic diagram illustrating an FRET experiment involving pCFP and pYFP as the fluorescence energy donor and acceptor, respectively, is utilized to measure the oligomer formation of ABCG2 in MCF7/ADR cells treated with 3.2 μM BIRB 796 or 100 μM anisomycin.(H and I) The FRET phenomenon occurs when the distance between pCFP and pYFP is within 10 nm. The color represents the degree of FRET efficiency. Scale bar: 50 μm. n = 33 cells for control group, n = 18 cells for anisomycin group, and n = 36 cells for BIRB 796 group. Data are mean ± SD, ∗∗p < 0.01, ∗∗∗p < 0.005.