Fig. 5: Cholesterol depletion through Methyl-β cyclodextrin in vivo stalls tumor growth in a STING-dependent manner. | Nature Communications

Fig. 5: Cholesterol depletion through Methyl-β cyclodextrin in vivo stalls tumor growth in a STING-dependent manner.

From: Cholesterol-binding motifs in STING that control endoplasmic reticulum retention mediate anti-tumoral activity of cholesterol-lowering compounds

Fig. 5

a C56BL/6 mice (n = 5) were inoculated with 1 × 106 MC38 colon adenocarcinoma cells on right flank and treated with various doses of MβCD by intratumoral injection on day 7, 10, and 13. Tumor growth is shown as mean ± SEM. b C56BL/6 mice (n = 8) with MC38 tumors were treated with high (30 mg/kg) and low (0.3 mg/kg) dose of MβCD by intratumoral injection on day 7, 10, and 13. Tumor growth is shown as mean ± SEM. The individual spaghetti plots can be seen in Supplementary Fig 9. Statistically significant differences were calculated using a two-way ANOVA with Geisser-Greenhouse correction followed by Holm–Sidak’s multiple comparisons test (**p < 0.01). c Kaplan–Meier plot depicting probability of survival in each of the treatment groups. Statistically significant difference was calculated using Mantel-Cox Log-rank test. (**p < 0.01). d Tumor volume measurements in C57BL/6 STING-deficient mice (n = 6) (the golden ticket strain) following same treatment regime as wildtype mice. Tumor growth is shown as mean ± SEM. e C56BL/6 mice (n = 8) with MC38 tumors were treated with MβCD (0.3 mg/kg) or 2′3′-cGAMP (1 µg/dosage), or the combination by intratumoral injection on day 10, 13, and 16. Tumor growth is shown as mean ± SEM. Statistically significant differences were calculated using two-way ANOVA with Holm–Sidak’s multiple comparisons test (**p < 0.01). f Immunoblot analysis of STING and TBK1 phosphorylation levels in tumors (n = 3 different mouse/group) from mice treated with MβCD (0.3 mg/kg) or 2′3′-cGAMP (1 µg/dosage), or the combination by intratumoral injection. g C56BL/6 mice (n = 5) with MC38 tumors were treated with three different treatment schemes on day 8, 11, and 14. Treatment consisted of (i) 0.3 mg/kg dose of MβCD delivered by intratumoral injection, (ii) 10 mg/kg anti-PD-1 antibody (RMP1-14) delivered as intraperitoneal injection, or (iii) a combination of MβCD and RMP1-14. Tumor growth is shown as mean ± SEM. Statistically significant differences were calculated using two-way ANOVA with Holm–Sidak’s multiple comparisons test (**p < 0.01; ****p < 0.0001). h Kaplan–Meier plot depicting probability of survival. Statistically significant difference was calculated using Mantel-Cox Log-rank test. (**p < 0.01).

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