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. 2021 May 13;7:103. doi: 10.1038/s41420-021-00486-0

Fig. 3. Inhibition of HIF1α and HIF2α increases tumour volume but promotes chemosensitization.

Fig. 3

A–C In the absence of TMZ, tumour volume and weight were decreased after HIF1α or HIF2α-KO individually compared with the empty vector control, but the dual HIF1α and HIF2α knockout group had a larger tumour volume and tumour weight than the other three groups. After TMZ treatment (2 mg/kg), the tumour volume decreased after HIF1α and HIF2α knockout individually or simultaneously, and the smallest tumour volume was observed in the group with dual HIF1α and HIF2α knockout. In addition, the group with dual HIF1α and HIF2α knockout had the lowest tumour weight among all the groups. D, E In the absence of TMZ, the survival time became longer after HIF1α or HIF2α knockout individually, but the survival time was shorter in the dual HIF1α and HIF2α knockout group than in the other three groups (median survival time of the empty vector group vs HIF1α-ko vs HIF2α-ko vs HIF1α/HIF2α-ko group = 26 vs 31 vs 27.5 vs 22 days). However, after TMZ treatment (2 mg/kg), the HIF1α or HIF2α knockout group experienced prolonged survival, and the longest survival time was observed in the group with dual HIF1α and HIF2α knockout (median survival time of the empty vector group vs HIF1α-ko vs HIF2α-ko vs HIF1α/HIF2α-ko group = 30 vs 35 vs 34 vs 41 days). F The above cells were cultured in 1% O2 for 72 h in the absence of TMZ, and there were no significant differences in cell proliferation between the HIF1α-KO, HIF2α-KO and control empty vector groups. However, after knocking out both HIF1α and HIF2α, the growth rate became the highest among all the groups. G The above cells were cultured in 1% O2 for 72 h, and TMZ (400 μM) was added to the culture medium for an additional 72 h. After HIF1α or HIF2α was knocked out individually, cell proliferation decreased. After both HIF1α and HIF2α were knocked out, the growth rate became the lowest among all the groups. H The above cells were cultured in 1% O2 for 72 h, and TMZ (400 μM) was added to the culture medium for an additional 72 h. The apoptosis rate increased after HIF1α or HIF2α knockout individually. After knocking out both HIF1α and HIF2α, the apoptosis rate became the highest among all the groups. The P value was determined by one-way ANOVA, and the survival time was analysed by the log-rank test.