Triptolide inhibits the progression of Glioblastoma U251 cells via targeting PROX1
BackgroundGlioblastoma 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 wilfordi...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-03-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1077640/full |
| _version_ | 1811155438104739840 |
|---|---|
| author | Chao Yuan Chao Yuan Yanli Liao Shengjie Liao Mi Huang Duanzhuo Li Weibin Wu Yi Quan Liqiang Li Liqiang Li Xin Yu Wenxia Si Wenxia Si |
| author_facet | Chao Yuan Chao Yuan Yanli Liao Shengjie Liao Mi Huang Duanzhuo Li Weibin Wu Yi Quan Liqiang Li Liqiang Li Xin Yu Wenxia Si Wenxia Si |
| author_sort | Chao Yuan |
| collection | DOAJ |
| description | BackgroundGlioblastoma 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.MethodsThe 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.ResultsWe 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.ConclusionThis study verified that TPL inhibited the progression of glioblastoma cells by transcriptionally depressing the expression of PROX1. |
| first_indexed | 2024-04-10T04:33:01Z |
| format | Article |
| id | doaj.art-8b050b86ffbd4fc5bd1d9014f36e5e01 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T04:33:01Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8b050b86ffbd4fc5bd1d9014f36e5e012023-03-10T05:33:57ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-03-011310.3389/fonc.2023.10776401077640Triptolide inhibits the progression of Glioblastoma U251 cells via targeting PROX1Chao Yuan0Chao Yuan1Yanli Liao2Shengjie Liao3Mi Huang4Duanzhuo Li5Weibin Wu6Yi Quan7Liqiang Li8Liqiang Li9Xin Yu10Wenxia Si11Wenxia Si12Department of Scientific Research and Experiment Center, Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaDepartment of Oncology, Zhaoqing First People’s Hospital Affiliated to Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaDepartment of Scientific Research and Experiment Center, Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaDepartment of Scientific Research and Experiment Center, Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaDepartment of Scientific Research and Experiment Center, Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaDepartment of Scientific Research and Experiment Center, Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaDepartment of Scientific Research and Experiment Center, Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaDepartment of Oncology, Zhaoqing First People’s Hospital Affiliated to Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaDepartment of Scientific Research and Experiment Center, Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaDepartment of Oncology, Zhaoqing First People’s Hospital Affiliated to Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaDepartment of Scientific Research and Experiment Center, Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaDepartment of Scientific Research and Experiment Center, Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaDepartment of Oncology, Zhaoqing First People’s Hospital Affiliated to Zhaoqing Medical College, Zhaoqing, Guangdong, ChinaBackgroundGlioblastoma 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.MethodsThe 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.ResultsWe 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.ConclusionThis study verified that TPL inhibited the progression of glioblastoma cells by transcriptionally depressing the expression of PROX1.https://www.frontiersin.org/articles/10.3389/fonc.2023.1077640/fulltriptolide (PubChem CID: 107985)Glioblastoma multiformePROX1, apoptosismigration and invasionproliferation |
| spellingShingle | Chao Yuan Chao Yuan Yanli Liao Shengjie Liao Mi Huang Duanzhuo Li Weibin Wu Yi Quan Liqiang Li Liqiang Li Xin Yu Wenxia Si Wenxia Si Triptolide inhibits the progression of Glioblastoma U251 cells via targeting PROX1 Frontiers in Oncology triptolide (PubChem CID: 107985) Glioblastoma multiforme PROX1, apoptosis migration and invasion proliferation |
| title | Triptolide inhibits the progression of Glioblastoma U251 cells via targeting PROX1 |
| title_full | Triptolide inhibits the progression of Glioblastoma U251 cells via targeting PROX1 |
| title_fullStr | Triptolide inhibits the progression of Glioblastoma U251 cells via targeting PROX1 |
| title_full_unstemmed | Triptolide inhibits the progression of Glioblastoma U251 cells via targeting PROX1 |
| title_short | Triptolide inhibits the progression of Glioblastoma U251 cells via targeting PROX1 |
| title_sort | triptolide inhibits the progression of glioblastoma u251 cells via targeting prox1 |
| topic | triptolide (PubChem CID: 107985) Glioblastoma multiforme PROX1, apoptosis migration and invasion proliferation |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1077640/full |
| work_keys_str_mv | AT chaoyuan triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 AT chaoyuan triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 AT yanliliao triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 AT shengjieliao triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 AT mihuang triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 AT duanzhuoli triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 AT weibinwu triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 AT yiquan triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 AT liqiangli triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 AT liqiangli triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 AT xinyu triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 AT wenxiasi triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 AT wenxiasi triptolideinhibitstheprogressionofglioblastomau251cellsviatargetingprox1 |