Figure 6

JNK is involved in maintaining the chemoresistance of acquired chemoresistant cancer cells by activating Gli. The data are expressed as the means ± s.d. from three independent experiments. A, Treatment with the peptide JNK inhibitor JIP circumvents the chemoresistance of K562/A02 cells to Dox. K562/A02 cells were seeded into 96-well plates, and incubated with vehicle control or Dox supplemented with or without JIP (2 μM) for 72 h. B, K562/A02 cells were treated with JIP (2 μM) for 24 h, and were collected for QT-PCR analysis of the expression of Gli1. C, Ectopic expression of JNK dominant negative mutant plasmid JNK1(APF) by lenti-virus approach enhances the sensitivity of K562/A02 cells to Dox. K562/A02 cells with stable expressions of JNK1(APF) and GFP were seeded into 96-well plates, and incubated with vehicle control or Dox for 72 h. D, K562/A02 cells with stable expressions of JNK1(APF) and GFP were collected for QT-PCR analysis of expression of Gli1. E, Activation of JNK in K562 cells by JNK constitutive mutant plasmid MKK7-JNK1 causes insensitivity of K562 cells to Dox, while inhibition of Gli activity by GANT58 recovers the sensitivity of K562 cells to Dox. K562 cells with forced expression of MKK7-JNK1, MKK7-JNK1(APF), GFP by lenti-virus approach were seeded in 96-well plates, and incubated with vehicle control or Dox supplemented with or without various GANT58 (10 μM) for 72 h. F, K562 cells with forced expression of MKK7-JNK1, MKK7-JNK1(APF), GFP by lenti-virus approach were harvested for QT-PCR analysis of Gli1 expressions.