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Page 18 of 25 Han et al. Cancer Drug Resist 2024;7:16 https://dx.doi.org/10.20517/cdr.2024.01

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Figure 8. (A) Expression of pdk1, RXRα, PPAα, and Bcl-2 RNA was detected using RT-qPCR ( P < 0.05, P < 0.01 vs. control group); (B)
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The viability of U251 cells after 12 and 24 h of TMZ treatment ( P < 0.05, P < 0.01, P < 0.001, P < 0.0001 vs. control group); (C)
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The viability of U251/TMZ resistant strains after 24 h of TMZ treatment ( P < 0.05, P < 0.001, P < 0.0001 vs. control group); (D)
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The viability of U251/TMZ resistant strains after 24 h of isocuB treatment ( P < 0.05, P < 0.001, **** P < 0.0001 vs. control group). RT-
qPCR: Reverse transcription-quantitative polymerase chain reaction; TMZ: temozolomide; isocuB: isocucurbitacin B.
materials as a promising strategy for developing novel medications . IsocuB belongs to the class of
[7]
terpenoids, which have been found to interact with a variety of signaling pathways, such as the MAPK,
nuclear factor κB (NF-κB), and glycolytic enzyme pathways . Namely, it is interesting to verify whether
[27]
IsocuB may have anti-glioma properties.

Network pharmacology integrates systems biology, pharmacology, and computational analysis techniques
[28]
to investigate the complex relationships between compounds, diseases, and targets . Our study revealed
280 overlapping target genes of isocuB and glioma. Through PPI analysis, the top five genes were RXRα,
AKT1, ESR1, MAPK1, and HSP90AA1. The GO and KEGG results revealed that the primary pathways
targeted by isocuB against glioma were the PI3K-AKT and MAPK signaling pathways. AKT1 and MAPK1