Fig. 3: Persistent TDO2 expression in CRPC also promotes tumour progression and drug resistance via the Kyn-AhR pathway. | Cell Discovery

Fig. 3: Persistent TDO2 expression in CRPC also promotes tumour progression and drug resistance via the Kyn-AhR pathway.

From: AR to GR switch modulates differential TDO2-Kyn-AhR signalling to promote the survival and recurrence of treatment-induced dormant cells in prostate cancer

Fig. 3

a TDO2 mRNA levels were analyzed in normal prostate tissues (n = 495) and prostate cancer tissues (n = 152) from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. b TDO2 mRNA expression levels in normal prostate tissues (n = 29), primary prostate cancer tissues (n = 128) and metastatic prostate cancer tissues from the GEO database (GSE21034) were analysed. The primary prostate cancer tissue was further analysed according to Gleason grade. c Analysis of TDO2 mRNA levels in CRPC cell lines from published single-cell sequencing results. d Immunohistochemical staining analysis was performed on the tissues of patients at low-grade (LG), high-grade (HG) and CRPC stages. The Q score was used to semi-quantify the TDO2 staining. e Western blotting was used to assess the protein expression levels of TDO2 and AhR in the prostate cancer cell lines LNCaP, C4-2, 22RV1, DU145 and PC3. f The protein expression levels of IDO1 in the prostate cancer cell lines LNCaP, C4-2, 22RV1, DU145 and PC3 were examined by Western blot, and PC3 + IFN-γ was used as the positive control for IDO1 expression. g An enzalutamide-resistant LNCaP cell line was established, and the protein levels of TDO2 and AhR were examined by western blotting assay. h–j TDO2 was knocked down by shRNA in LNCaP-EnzR cells, the protein levels of TDO2 and AhR were assessed (h), and cell proliferation, colony formation (i), and cell migration (j) were examined. k LNCaP-EnzR cells were treated with the TDO2 inhibitor 680C91 and the AhR inhibitor CH223191/BAY2416964 to assess cell inhibition. l The proliferation of LNCaP-EnzR cells treated with the TDO2 inhibitors 680C91 and 680C91+Kyn was examined on days 0, 1, 3, 5 and 7. m LNCaP-EnzR xenograft tumours were treated separately with a placebo, the TDO2 inhibitor LM10, the TDO2 inhibitor LM10 + Kyn, the AhR inhibitor CH223191, or the AhR inhibitor CH223191 + Kyn. The tumour weights were recorded (n = 4). n RNA from LNCaP-EnzR xenograft tumours was extracted, and the mRNA expression levels of CYP1A1 and CYP1B1 were assessed by RT‒qPCR (n = 6). *P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Back to article page