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. 2021 Aug 16;131(16):e146186. doi: 10.1172/JCI146186

Figure 8. Cancer-associated mesothelial cells promote ovarian cancer cell chemoresistance and ABC drug transporter activity through OPN, CD44, and PI3K/AKT signaling.

Figure 8

(A and B) Effect of the anti-CD44 blocking Ab and/or integrin-blocking RGD peptide on LP9-conditioned media–mediated cisplatin resistance (A) or sphere-formation increase (B) of OC8 cells. Each group is statistically compared with LP9-conditioned media plus control Ab plus RGE group (n = 3 or 4). (C) Western blot showing PI3K/AKT signaling in OC8 cells cocultured with LP9 shControl or LP9 shOPN cells. (D) Western blot showing PI3K/AKT signaling in OC8 cells treated with exogenous OPN and/or anti-CD44 blocking Ab. (E) Effect of PI3K/AKT pathway inhibitor LY294002 on OPN-mediated cisplatin resistance of OC8 cells. Each group is statistically compared with exogenous OPN–alone group (n = 4). (F) Fold increase of relative mRNA expression of ABC transporters in OC8 with LP9 coculture versus OC8 monoculture, as normalized to GAPDH mRNA in real-time PCR analysis (n = 3). (G and H) Multidrug resistance assay detecting the activity of major types of ABC transporters (MDR1, MRP, and BCRP) in OC8 cells treated with LP9-conditioned media and/or anti-OPN Ab. Cyan histograms show dye retention of untreated cell, and red histograms show dye retention of respective inhibitor-treated cells in G. The same untreated cells in cyan are used in each row of histograms. Multidrug resistance activity factor (MAF) indicative of corresponding ABC drug transporter activity is shown in H and statistically compared with LP9-conditioned media plus control Ab group (n = 3). (I and J) Multidrug resistance assay detecting ABC transporter activity in OC8 cells treated with LP9-conditioned media and/or anti-CD44 blocking Ab (I) or the PI3K/AKT inhibitor LY294002 (J). MAF indicates corresponding ABC protein activity and is statistically compared with LP9-conditioned media or LP9-conditioned media plus control Ab group (n = 3). Data are presented as mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001, 2-way ANOVA (A, B, E, and H–J) and 2-tailed Student’s t test (F).