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. 2018 Sep 17;7(11):5577–5588. doi: 10.1002/cam4.1770

Figure 4.

Figure 4

USP14 modulated sensitivity of GC cells to cisplatin through Akt/ERK signaling pathways. A, Blocking USP14 expression significantly reduced p‐Akt (T308/S473) and p‐ERK (T202/Y204) in MKN45 and KATO III cells. One representative result of two independent assays was shown here. B, p‐Akt (T308/S473) and p‐ERK (T202/Y204) were degraded by ubiquitin‐proteasome machinery. Treatment of 10 μmol/L MG132 for 4 h rescued these proteins from degradation in USP14‐deleted MKN45 and KATO III cells. One representative result of two independent assays was shown here. C, Pretreatment of 10 μmol/L LY294002 for 1 h reduced cisplatin IC50 from 7.967 ± 2.89 to 2.463 ± 1.79 μmol/L in MKN45 cells or from 13.78 ± 3.76 to 6.098 ± 2.03 μmol/L in KATO III cells, respectively. Similarly, PD98059 (10 μmol/L, pretreated for 1 h) cisplatin IC50 decreased from 7.967 ± 2.89 to 1.774 ± 0.18 μmol/L in MKN45 cells or from 13.78 ± 3.76 to 1.468 ± 1.85 μmol/L in KATO III cells, these cells which were pretreated with PD98059 for 1 h. DMSO was used as the negative control