Abstract
Background: Glioblastoma multiforme (GBM) is a heterogeneous and highly vascularized brain tumor that avoids apoptosis due to P-glycoprotein (P-gp) mediated multidrug resistance. Therefore, the development of new therapeutic strategies that induce apoptosis and inhibit proliferation is urgently warranted.
Objectives: We examined the efficacy of the combination of baicalin (BAI) and knockdown of miR-148a gene in human glioblastoma T98G and U87MG cell lines.
Methods: T98G and U87MG cells were transfected with miR148a siRNA. The influence of miR- 148a siRNA in combination with BAI on T98G and U87MG cell viability, proliferation, apoptosis, and autophagy was evaluated as well. Alterations in the mRNA expression of autophagy-related genes were analyzed using RT-qPCR.
Results: The transfection of T98G and U87MG cells with miR148a specific siRNA and exposition on baicalin led to a significant reduction in cell viability and proliferation, the accumulation of sub G1-phase cells and a reduced population of cells in the S and G2/M phases (only in U87MG cell line), increased population of cells in the S phase in T98G cell line and apoptosis or necrosis induction and induction of autophagy for both cell lines.
Conclusion: The siRNA-induced miR-148a mRNA knockdown in combination with baicalin may offer a novel therapeutic strategy to more effectively control the growth of human GBM cells. Thus, knockdown of this gene in combination with baicalin inhibits proliferation (cell cycle arrest in the S phase in T98G but not in U87MG cells), induces apoptosis, and regulates autophagy in T98G and U87MG cells. However, further studies are urgently needed to confirm a positive phenomenon for the treatment of GBM.
Keywords: Glioblastoma multiforme, baicalin, siRNA, miR148a, apoptosis, autophagy.
Graphical Abstract
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