Fig. 6

Intense ERS/UPR increases intracellular Oxaliplatin accumulation by down-regulating ABCC10 via IRE1α pathway. a High dose of Tm (10 µg/mL) treatment for 24 h clearly decreases ABCC10 in all 5 CRC cell lines. n = 3. ** P < 0.01, *** P < 0.001. Uncropped blots are provided in Supplementary information Fig. S15. b High dose of Tm (10 µg/mL) treatment for 24 h activates the IRE1α pathway of UPR and down-regulates ABCC10. While pre-treatment of STF-083010 (200 µM) for 1 h partly recovers ABCC10 expression. n = 3. ** P < 0.01, *** P < 0.001. Uncropped blots are provided in Supplementary information Fig. S16. c Oxaliplatin accumulation is significantly increased in response to Tm (10 µg/mL) in Caco-2 cells. While pre-treatment of STF-083010 (200 µM) decreased intracellular Oxaliplatin accumulation. n = 3. ** P < 0.01. d Tm (10 µg/mL) increases intracellular accumulation of Paclitaxel, a determined substrate of ABCC10, which is reversed by pre-treatment of STF-083010 (200 µM). n = 3. ** P < 0.01. e ABCC10 mRNA contains the CUGCAA consensus sequence which forms a hairpin structure predicted by RNAfold Web server. f ABCC10 mRNA level is significantly decreased when exposed to Tm (10 µg/mL). Additional STF treatment restores ABCC10 mRNA level up to 8 h. n = 3. *** P < 0.001. Tm denotes Tunicamycin, STF denotes STF-083010