Fig. 7: Combined treatment with 6-MP and TMZ blocks TMZ-induced DNA damage repair and synergistically inhibits brain tumor growth. | Nature Communications

Fig. 7: Combined treatment with 6-MP and TMZ blocks TMZ-induced DNA damage repair and synergistically inhibits brain tumor growth.

From: Hypoxanthine phosphoribosyl transferase 1 metabolizes temozolomide to activate AMPK for driving chemoresistance of glioblastomas

Fig. 7: Combined treatment with 6-MP and TMZ blocks TMZ-induced DNA damage repair and synergistically inhibits brain tumor growth.

a and b Cells were treated with 0.2 mM of 15N-TMZ together with the indicated concentration of 6-MP for 2 h. Intracellular 15N-AICA (a) and 15N-AICAR levels (b) were measured by HPLC-MS. Data represent the mean ± SD from sextuplicate experiments. **P < 0.001. c Synergistic effect of TMZ with 6-MP on U87 (gray circle), and MES28 (orange circle). CI (combination index) value was calculated. d Luciferase-expressing MES28 and U87 cells were intracranially injected into nude mice (n = 10 for each group). Shown are luminescence intensity of tumors in representative mice at the indicated time points. e The survival time of the indicated groups of mice was recorded. **P < 0.001. f–h, Representative IHC images of ACC1 pS79 (f), RRM1 pT52 (g), and γ-H2AX (h) were shown. Scale bars, 60 μm. n = 10 for each group. i Representative TUNEL images were shown. Scale bars, 60 μm. n = 10 for each group. Statistics: a, b unpaired Student’s t-test for two-group comparison. e Log-rank test for two-group comparison (TMZ vs. TMZ + 6-MP). Source data are provided as a Source Data file.

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