Fig. 3: Efficacy of an autophagy inhibitor and chemotherapy.
From: Early tolerance and late persistence as alternative drug responses in cancer
a Viability of five PDOs from mCRC patients treated with FOLFOX, FOLFIRI, and ULK1i (SBI-0206965). Each dot represents the measurement of a single organoid after one week of treatment. Significant differences among groups calculated by applying a two-sided Student’s t-test (mean ± SD) (exact P values are indicated in figure; ****P < 0.0001). b Tumour growth curves of HCT116 cells subcutaneously transplanted in immunocompromised mice (n = 8 mice per group). Mice were treated twice a week for two weeks with FOLFOX or FOLFIRI alone or in combination with ULK1i. Tumour volume was measured twice a week and significant differences among groups calculated by applying a two-sided Student’s t-test (mean ± SEM). A population genetics model describing tumour growth during treatment. A decrease in growth rate occurred with respect to the CTRL sample in mice treated with ULK1i, FOLFOX, FOLFOX+ULK1i, FOLFIRI and FOLFIRI+ULK1i (c) (n = 8 per group; median; whiskers: min to max; first and third quartile are shown). Growth curves of synergistic and additive inhibition for the combinatorial treatments (d). e, f Quantification of immunohistochemistry analysis for Ki67 and γH2AX performed on tumours after two weeks of treatment. Three different areas of each tumour slide were considered and significant differences among groups were calculated by an ANOVA followed by Bonferroni post-test (n = 21; median; whiskers: min to max; 25th and 75th percentiles are shown; ****P < 0.0001). g Quantification of viability of MDA-MB-231 and MBC26 breast cancer cells treated with cisplatin and ULK1i after one week (MDA-MB-231 - n = 7; mean ± SD) or three days (MBC26 - n = 3; mean ± SD). Differences among groups were calculated by ANOVA followed by Tukey post-test (exact P values are indicated in figure; ****P < 0.0001). h Cell viability of two primary cancer models of ovarian cancer treated with carboplatin and paclitaxel and ULK1i (n = 3 to 4 experimental replicates; mean ± SD). Differences among groups were calculated by a two-sided Student’s t-test (exact P values are indicated in figure; ****P < 0.0001). Source data are provided as a Source Data file.
