The PI3K Inhibitor XH30 Enhances Response to Temozolomide in Drug-Resistant Glioblastoma via the Noncanonical Hedgehog Signaling Pathway Article Swipe
Ming Ji
,
Zhihui Zhang
,
Songwen Lin
,
Chunyang Wang
,
Jing Jin
,
Nina Xue
,
Heng Xu
,
Xiaoguang Chen
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3389/fphar.2021.749242
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3389/fphar.2021.749242
Glioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system. Temozolomide (TMZ)–based adjuvant treatment has improved overall survival, but clinical outcomes remain poor; TMZ resistance is one of the main reasons for this. Here, we report a new phosphatidylinositide 3-kinase inhibitor, XH30; this study aimed to assess the antitumor activity of this compound against TMZ-resistant GBM. XH30 inhibited cell proliferation in TMZ-resistant GBM cells (U251/TMZ and T98G) and induced cell cycle arrest in the G1 phase. In an orthotopic mouse model, XH30 suppressed TMZ-resistant tumor growth. XH30 was also shown to enhance TMZ cytotoxicity both in vitro and in vivo . Mechanistically, the synergistic effect of XH30 may be attributed to its repression of the key transcription factor GLI1 via the noncanonical hedgehog signaling pathway. XH30 reversed sonic hedgehog–triggered GLI1 activation and decreased GLI1 activation by insulin-like growth factor 1 via the noncanonical hedgehog signaling pathway. These results indicate that XH30 may represent a novel therapeutic option for TMZ-resistant GBM.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fphar.2021.749242
- https://www.frontiersin.org/articles/10.3389/fphar.2021.749242/pdf
- OA Status
- gold
- Cited By
- 11
- References
- 51
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3216714987
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- OpenAlex ID
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https://openalex.org/W3216714987Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3389/fphar.2021.749242Digital Object Identifier
- Title
-
The PI3K Inhibitor XH30 Enhances Response to Temozolomide in Drug-Resistant Glioblastoma via the Noncanonical Hedgehog Signaling PathwayWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-11-26Full publication date if available
- Authors
-
Ming Ji, Zhihui Zhang, Songwen Lin, Chunyang Wang, Jing Jin, Nina Xue, Heng Xu, Xiaoguang ChenList of authors in order
- Landing page
-
https://doi.org/10.3389/fphar.2021.749242Publisher landing page
- PDF URL
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https://www.frontiersin.org/articles/10.3389/fphar.2021.749242/pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.frontiersin.org/articles/10.3389/fphar.2021.749242/pdfDirect OA link when available
- Concepts
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Temozolomide, GLI1, Hedgehog signaling pathway, Cancer research, PI3K/AKT/mTOR pathway, Signal transduction, Cell cycle, Pharmacology, Medicine, Chemistry, Biology, Glioma, Cell biology, Internal medicine, CancerTop concepts (fields/topics) attached by OpenAlex
- Cited by
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11Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 4, 2023: 2, 2022: 2Per-year citation counts (last 5 years)
- References (count)
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51Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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