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Fig. 5 | BMC Cancer

Fig. 5

From: Intense endoplasmic reticulum stress (ERS) / IRE1α enhanced Oxaliplatin efficacy by decreased ABCC10 in colorectal cancer cells

Fig. 5

Intense ERS/UPR significantly reduces CRC cell viability, promotes apoptosis and sensitizes CRC cells to Oxaliplatin. a High dose of Tm (10 µg/mL) treatment for 4 h, 8 h, 12 h and 24 h increases GRP78 and activates IRE1α pathway. n = 3. * P < 0.05, ** P < 0.01, *** P < 0.001. Uncropped blots are provided in Supplementary information Fig. S13. b The cellular viability of CRC cells exposed to Tm (10 µg/mL) are remarkably decreased. The additional ERS inhibitor 4-PBA (5 mM) can’t effectively restore the viability. n = 6. * P < 0.05, ** P < 0.01, *** P < 0.001. c Unlike on the CRC cells, high dose of Tm (10 µg/mL) has no obvious inhibitory effect on the normal human colonic epithelial NCM460 cells; while 4-PBA (5 mM) significantly inhibits their viability. Moreover, the viability of NCM460 cells is kept restrained when co-treated with 4-PBA and Tm. n = 6. Compared with DMSO * P < 0.05, ** P < 0.01, *** P < 0.001; Compared with Tm # P < 0.05, ### P < 0.001. d The pro-apoptotic factor CHOP in RKO cells is profoundly increased by high dose of Tm (10 µg/mL) for 4, 8, 12 and 24 h, while kept hypo-expressed upon the treatment of low dose of Tm (0.5, 1 and 2 µg/mL) for 24 h. n = 3. ** P < 0.01, *** P < 0.001. Uncropped blots are provided in Supplementary information Fig. S14. e The intense ERS/UPR induced by high dose of Tm (10 µg/mL) significantly accelerates the CRC cell apoptosis; but the mild ERS/UPR induced by low dose of Tm (0.5, 1 and 2 µg/mL) has no such effect. n = 3. * P < 0.05. f The CRC cells are treated with a gradient of Oxaliplatin (10, 20, 40, 80 and 160 ng/mL) for 24 h. Compared with the Oxaliplatin-treated cells, the cell viability is significantly declined in the presence of Tm (10 µg/mL). However, the pre-treatment of STF-083010 (200 µM) for 1 h to block the IRE1α pathway, the declined cell viability is recovered. n = 6. Compared with Oxa. *** P < 0.001; compared with Oxa. + Tm ## P < 0.01, ### P < 0.001. Oxa. denotes Oxaliplatin; Tm denotes Tunicamycin, STF denotes STF-083010

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