Extended Data Fig. 5: Inactivation of enteric neurons inhibits colorectal tumor growth.

(a) ChAT⁺ nerve fibers in SW480 rectal tumors in male Nude mice. n = 3 mice. (b-d) BTXA treatment in male Nude CDX model with injection of SW480 cells. BTXA rectal injections once every week for three cycles. Tumor morphology (b), weight (c), and volume (d). n = 6 mice per group. (e) tdTomato⁺ cholinergic nerve fibers in sciatic nerve tumors in male ChAT-Cre/Ai14 mice. n = 3 mice. (f-h) Sciatic nerve CDX model with injection of CMT93 cells. BTXA injections in sciatic nerve once every week for three cycles. Tumor morphology (f), weight (g), and volume (h). n = 10 tumors from 5 mice per group. (i) BTXA treatment for 24 hours on CRC cell viability. n = 7 biological replicates per group for SW480 and DLD-1; n = 5 biological replicates per group for MC38 and CMT93. (j-l) Combined chemogenetic activation of LS^GABA neurons and BTXA treatment in female C57BL/6 J CDX model with CNO intraperitoneal and BTXA intratumoral injection every four days. Tumor morphology (j), weight (k), and volume (l). n = 5, 6, 6, 6 mice for Control+Saline, hM3Dq+Saline, Control+BTXA, hM3Dq+BTXA respectively. Data are presented as mean ± SEM. Two-tailed Mann Whitney test (c-d, g-h, SW480 cells in i), two-tailed unpaired student’s t test (DLD-1, MC38 and CMT93 cells in i), Ordinary one-way ANOVA with Tukey’s multiple comparisons test (k) or with BKY two-stage FDR correction (l) are used. n.s., not significant.

Source data