Periostin Secreted by Carcinoma-Associated Fibroblasts Promotes Ovarian Cancer Cell Platinum Resistance Through the PI3K/Akt Signaling Pathway

Figures

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  Figure 1.. Expression of periostin in ovarian cancer stroma. (A) Analysis results based on GSE40595 data show that periostin transcription levels were increased significantly in ovarian cancer stroma (N = 31) compared with normal ovarian stroma (N = 8). (B) Periostin transcription levels were increased significantly in ovarian cancer stroma (N = 31) compared with tumor epithelial component (N = 32) in GSE40595 chip data. (C) IHC analysis shows that the periostin expression is upregulated in human ovarian stroma compared with normal ovarian stroma. ***P < 0.001

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  Figure 2.. Periostin reduces DDP-induced apoptosis in ovarian cancer cells. (A, B) Flow cytometry analysis was used to detect the apoptosis rate of ES-2 and SKOV-3 cells treated with DDP(10 µg/mL) and periostin. (C, E) CCK-8 assay showed periostin can reduce the inhibition rate of ES-2 and SKOV-3 cells after DDP treatment. (D, F) Periostin increases the IC50 value of DDP(10 µg/mL) in SKOV-3 and ES-2 cells. (G, H) Periostin increases the Bcl-2/BAX ratio of DDP(10 µg/mL) treated SKOV-3 and ES-2 cells. *P < 0.05, **P < 0.01.

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  Figure 3.. Periostin inhibits platinum-induced apoptosis in ovarian cancer cells by activating the PI3K/AKT pathway. (A, B) Flow cytometry assay showed that PI3K/AKT pathway-specific inhibitor Ly294002 could reverse the DDP (10 µg/mL) resistance of ES-2 and SKOV-3 cells induced by periostin. (C, D) Ly294002 increased the inhibition of ES-2 and SKOV-3 cells treated with DDP (10 µg/mL) and periostin. *P < 0.05. **P < 0.01.

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  Figure 4.. Periostin increases the BCL-2/BAX ratio of ovarian cancer cells after DDP treatment, and Ly294002 can reverse this effect. (A, B) Ly294002 reduced the Bcl-2/BAX ratio of DDP (10 µg/mL) and periostin-treated SKOV-3 and ES-2 cells. **P < 0.01.

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  Figure 5.. Periostin increases the phosphorylation of AKT in SKOV-3 and ES-2 cells, and this process can be blocked by LY294002. (A-D) Western blot analysis showed the phosphorylation level of AKT increased after periostin treatment, and LY294002 can block this change in both ovarian cancer lines. *P < 0.05, **P < 0.01.

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  Figure 6.. Periostin protein secreted by fibroblasts can reduce the sensitivity of ovarian cancer cells to DDP in the co-culture system. (A, B) RT-PCR and western blot assay certified that periostin expression increased in the POSTN OE MRC-5 group and decreased in the POSTN KD group. (C, D) Apoptosis of SKOV-3 and ES-2 cells induced by DDP (10 µg/mL) decreased when co-cultured with periostin OE MRC-5 cell. (E, F) Co-cultured with periostin OE MRC-5 cell could reduce the Bcl-2/BAX ratio of SKOV-3 and ES-2 cells after DDP treatment. *P < 0.05, **P < 0.01.