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Triptolide inhibits the progression of Glioblastoma U251 cells via targeting PROX1
Chao Yuan1,2, Yanli Liao1, Shengjie Liao1
1Department of Scientific Research and Experiment Center, Zhaoqing Medical College, Zhaoqing, Guangdong, China.
Background:
Glioblastoma multiforme (GBM) is the most lethal brain cancer in adults, characterized by rapid growth, extensive invasiveness, and poor prognosis, and there is still a lack of effective treatments. Here, we aimed to explore the role of triptolide (TPL), purified from Tripterygium wilfordii Hook F, on glioblastoma cell growth, apoptosis, proliferation, migration and invasion, as well as potential underlying mechanisms.
Methods:
The publicly available clinical data of Brain Lower Grade Glioma (LGG) from The Cancer Genome Atlas (TCGA) had been screened to observe PROX1 expression. The Kaplan-Meier analysis was used to analyze the relationship between PROX1 expression and GBM prognosis. CCK8, cell cycle, EDU, apoptosis, wound healing, and transwell assays were performed to detect the effects of TPL on glioblastoma U251 cell viability, cell cycle, proliferation, apoptosis, migration and invasion, respectively. Further, a soft agar colony assay was used to calculate the growth of glioblastoma cells. The qRT-PCR and western blot were conducted to quantify PROX1 mRNA and protein levels. The transcriptional regulation of TPL was detected by Dual luciferase reporter assay.
Results:
We found that TPL inhibited glioblastoma cell viability, proliferation, cell cycle, migration and invasion, but enhanced apoptosis in a dose-dependent manner. The expression of cell cycle inhibitor, P21, and pro-apoptosis factor, Bax was increased, while invasion-related factors MMP2 and MMP9 were silenced after TPL treatments. Mechanistically, TPL showed transcriptional inhibition of PROX1 appearance. Moreover, ectopic expression of PROX1 partially rescued the effects of TPL on glioblastoma cell viability, proliferation, apoptosis, migration and invasion, and on the expression of cell function-related genes.
Conclusion:
This study verified that TPL inhibited the progression of glioblastoma cells by transcriptionally depressing the expression of PROX1.
Insights
Triptolide (TPL) effectively inhibits glioblastoma (GBM) progression by suppressing PROX1 expression. This natural compound reduces GBM cell growth, migration, and invasion while promoting apoptosis, offering a potential therapeutic avenue.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain cancer with limited treatment options.
- Triptolide (TPL), derived from *Tripterygium wilfordii*, is investigated for its anti-cancer properties.
Purpose of the Study:
- To investigate the effects of TPL on glioblastoma cell growth, apoptosis, proliferation, migration, and invasion.
- To elucidate the underlying molecular mechanisms, focusing on PROX1 expression.
Main Methods:
- Analysis of TCGA data for PROX1 expression in gliomas.
- In vitro assays (CCK8, cell cycle, EDU, apoptosis, wound healing, Transwell, soft agar) to assess TPL's effects on U251 glioblastoma cells.
- qRT-PCR, Western blot, and dual luciferase reporter assays to determine PROX1 regulation by TPL.
Main Results:
- TPL dose-dependently inhibited glioblastoma cell viability, proliferation, cell cycle progression, migration, and invasion.
- TPL increased apoptosis and the expression of P21 and Bax, while decreasing MMP2 and MMP9.
- TPL transcriptionally inhibited PROX1, and PROX1 overexpression partially reversed TPL's effects.
Conclusions:
- Triptolide demonstrates significant anti-glioblastoma activity.
- The mechanism involves the transcriptional downregulation of PROX1 by TPL, inhibiting GBM progression.
