Research Paper Volume 13, Issue 4 pp 5284—5296

Matrix stiffness promotes glioma cell stemness by activating BCL9L/Wnt/β-catenin signaling

Suppressing Wnt/β-catenin signaling enhanced the anticancer effects of chemotherapy and radiotherapy. (A) Left: Survival of LN229 cells treated with different concentrations of temozolomide (TMZ; 0, 10, 50 or 100 mM) combined with PBS or gigantol (100 μM) on 16-kPa stiffness gels for 48 hours. Right: Survival of LN229 cells treated with different doses of radiotherapy (0, 2, 4, 6 or 10 Gy) combined with PBS or gigantol (100 μM) on 16-kPa stiffness gels. (B) Left: Survival of T98G cells treated with different concentrations of TMZ (0, 10, 50 or 100 mM) combined with PBS or gigantol on 16-kPa stiffness gels for 48 hours. Right: Survival of T98G cells treated with different doses of radiotherapy (0, 2, 4, 6 or 10 Gy) combined with PBS or gigantol (100 μM) on 16-kPa stiffness gels. (C, D) Tumor volumes (C) and survival (D) were analyzed at various time points in LN229-bearing mice treated with PBS, TMZ (10 mg/kg), gigantol (10 mg/kg) or TMZ (10 mg/kg) combined with gigantol (10 mg/kg). (E, F) Tumor volumes (E) and survival (F) were analyzed at various time points in LN229-bearing mice treated with PBS, radiotherapy (10 Gy), gigantol (10 mg/kg) or radiotherapy (10 Gy) combined with gigantol (10 mg/kg). (G, H) Tumor volumes (G) and survival (H) were analyzed at various time points in mice injected with LN229 cells that had been cultured on 16-kPa stiffness gels and treated with PBS, TMZ (10 mg/kg), gigantol (10 mg/kg) or TMZ (10 mg/kg) combined with gigantol (10 mg/kg). (I, J) Tumor volumes (I) and survival (J) were analyzed at various time points in mice injected with LN229 cells that had been cultured on 16-kPa stiffness gels and treated with PBS, radiotherapy (10 Gy), gigantol (10 mg/kg) or radiotherapy (10 Gy) combined with gigantol (10 mg/kg). (K, L) Tumor volumes (K) and survival (L) were analyzed at various time points in T98G-bearing mice treated with PBS, TMZ (10 mg/kg), gigantol (10 mg/kg) or TMZ (10 mg/kg) combined with gigantol (10 mg/kg). (M, N) Tumor volumes (M) and survival (N) were analyzed at various time points in U87-bearing mice treated with PBS, TMZ (10 mg/kg), gigantol (10 mg/kg) or TMZ (10 mg/kg) combined with gigantol (10 mg/kg). *P

Figure 4. Suppressing Wnt/β-catenin signaling enhanced the anticancer effects of chemotherapy and radiotherapy. (A) Left: Survival of LN229 cells treated with different concentrations of temozolomide (TMZ; 0, 10, 50 or 100 mM) combined with PBS or gigantol (100 μM) on 16-kPa stiffness gels for 48 hours. Right: Survival of LN229 cells treated with different doses of radiotherapy (0, 2, 4, 6 or 10 Gy) combined with PBS or gigantol (100 μM) on 16-kPa stiffness gels. (B) Left: Survival of T98G cells treated with different concentrations of TMZ (0, 10, 50 or 100 mM) combined with PBS or gigantol on 16-kPa stiffness gels for 48 hours. Right: Survival of T98G cells treated with different doses of radiotherapy (0, 2, 4, 6 or 10 Gy) combined with PBS or gigantol (100 μM) on 16-kPa stiffness gels. (C, D) Tumor volumes (C) and survival (D) were analyzed at various time points in LN229-bearing mice treated with PBS, TMZ (10 mg/kg), gigantol (10 mg/kg) or TMZ (10 mg/kg) combined with gigantol (10 mg/kg). (E, F) Tumor volumes (E) and survival (F) were analyzed at various time points in LN229-bearing mice treated with PBS, radiotherapy (10 Gy), gigantol (10 mg/kg) or radiotherapy (10 Gy) combined with gigantol (10 mg/kg). (G, H) Tumor volumes (G) and survival (H) were analyzed at various time points in mice injected with LN229 cells that had been cultured on 16-kPa stiffness gels and treated with PBS, TMZ (10 mg/kg), gigantol (10 mg/kg) or TMZ (10 mg/kg) combined with gigantol (10 mg/kg). (I, J) Tumor volumes (I) and survival (J) were analyzed at various time points in mice injected with LN229 cells that had been cultured on 16-kPa stiffness gels and treated with PBS, radiotherapy (10 Gy), gigantol (10 mg/kg) or radiotherapy (10 Gy) combined with gigantol (10 mg/kg). (K, L) Tumor volumes (K) and survival (L) were analyzed at various time points in T98G-bearing mice treated with PBS, TMZ (10 mg/kg), gigantol (10 mg/kg) or TMZ (10 mg/kg) combined with gigantol (10 mg/kg). (M, N) Tumor volumes (M) and survival (N) were analyzed at various time points in U87-bearing mice treated with PBS, TMZ (10 mg/kg), gigantol (10 mg/kg) or TMZ (10 mg/kg) combined with gigantol (10 mg/kg). *P < 0.05, **P < 0.01, n.s. no significant difference.