FIGURE 1 from Activation of the Mevalonate Pathway in Response to Anti-cancer Treatments Drives Glioblastoma Recurrences Through Activation of Rac-1

Combination therapies that converge on the immediate-early response to radiation through the MAPK cascade universally upregulate the mevalonate pathway. A and C, Western blotting of p-ERK, total ERK, p-P38, and total P38 in patient-derived GBM HK374 and HK217 cell lines upon radiation (RT) in combination with QTP (10 µmol/L) or TMZ (1 mmol/L) or vincristine (250 nmol/L) at 2 hours after treatment. B and D, The densitometry measurements of p-ERK/total ERK and p-P38/total P38 using Image J. E, Heat map showing the results of qRT-PCR for the cholesterol biosynthesis–related genes in both HK374 and HK217 cells treated with radiation in the presence or absence of TMZ (1 mmol/L) for 2 consecutive days. F, Heat map showing the results of qRT-PCR for the cholesterol biosynthesis–related genes in both HK374 and HK217 cells treated with radiation in the presence or absence of vincristine (250 nmol/L) for 24 hours. G, Heat map showing the results of qRT-PCR for the cholesterol biosynthesis–related genes in both HK374 and HK217 cells treated with radiation in the presence or absence of QTP (10 µmol/L) for 2 consecutive days. All experiments have been performed with at least three biological independent repeats. P-values were calculated using one-way ANOVA. The P-values listed in the heat maps were from the comparison of RT + DMSO with RT + TMZ (E) or RT + Vincristine (F) or RT + QTP (G). *, P < 0.05; **, P < 0.01; ***, P < 0.001.