Retracted: Triptolide inhibits the proliferation and migration of medulloblastoma Daoy cells by upregulation of microRNA‐138

Abstract

Medulloblastoma is a primitive neuroectodermal-derived brain tumor and the most common malignant brain tumor in children. Triptolide (TPL) is the major active component extracted from Tripterygium wilfordii Hook F. This study aimed to explore the effects of TPL on medulloblastoma cell proliferation, migration, and apoptosis, as well as the underlying possible molecular mechanism. Viability, proliferation, and apoptosis of Daoy cells were measured using cell counting kit-8 assay, 5-bromo-2'-deoxyuridine incorporation assay, and Guava Nexin assay, respectively. Cell migration was detected using two-chamber transwell assay and wound healing assay. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to determine the relative expression of microRNA-138 (miR-138) in Daoy cells. Cell transfection was used to change the expression of miR-138 in cells. Western blot analysis was used to analyze the expression of key factors involved in cell apoptosis, cell migration, the phosphatidylinositol 3-kinase (PI3K)/protein kinase 3 (AKT) pathway, and the Notch pathway in Daoy cells. We found that TPL significantly inhibited the viability, proliferation, and migration of Daoy cells but promoted Daoy cell apoptosis. The expression levels of matrix metalloproteinases (MMP)-2 and MMP-9 after TPL treatment were decreased. The expression of miR-138 in Daoy cells after TPL treatment was increased. Suppression of miR-138 obviously reversed the TPL-induced Daoy cell proliferation, migration inhibition, and cell apoptosis enhancement, as well as the inactivation of the PI3K/AKT and Notch pathways. Cyclin-dependent kinase 6 (CDK6) was a direct target gene of miR-138, which might be involved in the antitumor effects of TPL on Daoy cells. In conclusion, our study verified that TPL exerted anticancer effects on medulloblastoma cells possibly via upregulating miR-138 and inactivating the PI3K/AKT and Notch pathways.

Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120

“…Migration of MG63 and U2OS cells was measured using a two-chamber migration assay (Corning Incorporated, New York, NY) with 8 lm pore filters as earlier described [23]. The incubation time was 48 h. Migrated cells in the lower chamber were stained using 0.5% crystal violet solution (Beyotime Biotechnology) and counted under microscope (40Â, Nikon).…”

Integrative analysis of gene expression and DNA methylation through one‐class logistic regression machine learning identifies stemness features in medulloblastoma

“…These compounds include the CDK inhibitors palbociclib and alvocidib, the AMPK inhibitor dorsomorphin, the IKK inhibitor BMS‐345541, the smoothened receptor antagonist cyclopamine, the topoisomerase inhibitors topotecan and doxorubicin, the GABA receptor agonist ivermectin, the NF‐κB pathway inhibitor auranofin, the MTOR inhibitor dactolisib, the AKT inhibitors MK‐2206 and pyrvinium‐pamoate, the HMGCR inhibitor simvastatin, the HDAC inhibitors apicidin, vorinostat, and givinostat, and the DNA synthesis inhibitor anisomycin. In addition, the survivin inhibitor YM155 (Brun et al ., ), the AKT inhibitor pyrvinium (Li et al ., ), and the RNA polymerase inhibitor triptolide (Zhang et al ., ) have been shown to exert anticancer effects on MB cells, although there were no results regarding effects on MB stem cells. More importantly, the CMap analysis identified the PI3K inhibitor GDC‐0941, which has been demonstrated to target CD133‐positive stem cell‐like MB subpopulations (Ehrhardt et al ., ).…”

Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives

“…Furthermore, triptolide can also achieve anticancer effects by regulating microRNAs. Haifang Zhang et al found that triptolide can inhibit the PI3K/AKT and Notch pathways, thereby exerting an anticancer effect on medulloblastoma cells 39 . Similarly, studies have shown that triptolide can increase the expression of microRNA-181a, which participates in the proliferation, migration and apoptosis of SH-SY5Y cells, thereby exerting a tumor-suppressing effect 40 .…”