The Toxic Effect and Mechanism of TMZ Combined with siHOXB9 on Glioblastoma Cells.

Glioblastoma (GBM) represents a highly invasive primary malignant tumor within the central nervous system (CNS). Temozolomide (TMZ), a first-line chemotherapy agent for GBM treatment, has significant limitations, including drug resistance, poor water solubility, a short half-life, and notable toxic side effects. The innovation of the TMZ dosage form is pivotal for enhancing its therapeutic efficacy. In this study, solid lipid nanoparticles (SLN) loaded with Angiopep-2 (A2) and TMZ (TMZ-A2SLN), a nanopolymer featuring a solid spherical morphology and a particle size of approximately 100 nm, were constructed. The combined effect of TMZ-A2SLN and small-interfering RNA (siRNA) that can knock down the expression of the HOXB9 gene (siHOXB9) augmented the sensitivity of the glioma cell line U251 to TMZ. Under the combined effect, the viability of U251 cells was reduced by 77%. Meanwhile, the mortality rate increased by approximately 45%, and the cell apoptosis rate rose by around 36%. The number of cells arrested in the G2/M and S phases rose. Proteomic analysis indicates that TMZ-A2SLN might be implicated in the pro-inflammatory signaling cascade, tumor migration, invasion, and angiogenesis during the treatment of glioma cells. Moreover, HOXB9 may play a crucial regulatory role in the PPAR signaling pathway, the neural signaling pathway, the phospholipase D signaling pathway, the IL-17 signaling pathway, mineral absorption, and other pathways during glioma cell treatment.