Fig. 9.

Antitumor activity of erastin and celastrol cotreatment on xenograft models of NSCLC. (A) Nude mice were injected subcutaneously with indicated HCC827 cells. Images of isolated tumors from nude mice treated with single‐agent erastin (5 mg·kg⁻¹), celastrol (1 mg·kg⁻¹), and their combination. Tumor volumes (B) and weights (C) of HCC827 xenografts in each treatment group are shown. (D) Tumor lysates were subjected to western blotting for HSF1, HSP27, LC3, and Parkin. (E) H&E staining tissue images obtained from major organs of erastin or/and celastrol‐treated mice for the in vivo toxicity evaluation. Scale bar, 100 µm. (F) HSF1 knockdown HCC827 cells were more sensitive to erastin and celastrol cotreatment in vivo. Representative images of subcutaneous tumors in mice inoculated with stable HSF1 knockdown HCC827 cells compared with the control group. Tumor volumes (G) and weights (H) of subcutaneous tumors in mice inoculated with stable HSF1 knockdown or SCR HCC827 cells. (I) Western blotting was performed to examine HSF1, HSP27, LC3, and Parkin protein expression in subcutaneous tumors. (J) Proposed mechanism of celastrol‐ and erastin‐induced cell death in NSCLC. The mean ± SD is shown, n = 6. Statistical significance was determined using one‐way or two‐way ANOVA with Tukey’s post hoc test. ***P < 0.001.