RNA interference targeting Aurora-A sensitizes glioblastoma cells to temozolomide chemotherapy

Abstract

Clinically, temozolomide (TMZ) is widely used in glioblastoma (GBM) treatment. However, the toxicity of TMZ may influence the quality of patient life. Thus, novel treatment options for sensitizing GBM cells to TMZ chemotherapy are necessary. Aurora-A is widely expressed in GBM and correlated with poor prognosis. It has been proven to be an effective target for gene therapy and chemotherapy. In the present study, short hairpin (sh)RNA targeting Aurora-A was employed to knockdown Aurora-A expression in GBM cells. Cell Counting Kit-8 assays, flow cytometry, colony formation assays, invasion assays and tube formation assays were used to determine the effects of Aurora-A knockdown when combined with TMZ treatment. A U251 subcutaneous cancer model was established to evaluate the efficacy of combined therapy. The results of the present study indicated that the proliferation, colony formation, invasion and angiogenesis of GBM cells were significantly inhibited by combined therapy when compared with TMZ treatment alone. In vivo results demonstrated that knockdown of Aurora-A significantly (P=0.0084) sensitizes GBM cells to TMZ chemotherapy. The results of the present study demonstrated that knockdown of Aurora-A in GBM cells enhances TMZ sensitivity in vitro and in vivo. Therefore, Aurora-A knockdown may be a novel treatment option for decreasing TMZ toxicity and improving patient quality of life.

Quantum Dots-siRNA Nanoplexes for Gene Silencing in Central Nervous System Tumor Cells

“…The siRNAs-based RNAi technology has brought potential promises for patients to fight against this deadly disease by gene therapy approach (Gan et al, 2016). Great efforts have been made by the medicine research community to seek effective gene targets for treating glioblastoma and several strategies have been proposed and identified (Zorzan et al, 2015).…”

“…The siRNA is sequenced to the target gene and able to arouse a sequence-specific gene silencing in post-transcription level. In the past years, RNAi-based cancer gene therapy has been extensively explored (Maduri, 2015; Gan et al, 2016). The success of RNAi therapeutic approach depends on two important factors, namely, efficient therapeutic targets and the delivery efficiency.…”

The Codelivery of siRNA and QDs by pH-Responsive Micelle for Hepatoma Cancer Cells

“…The invention of RNAi has brought promises for gene therapy of cancer by using small interfering RNA (siRNA), which selectively silences specific targets (Seyhan, 2011). In the past few years, RNAi-based cancer gene therapy has been extensively explored (Lin et al, 2013; Maduri, 2015; Gan et al, 2016; Lin et al, 2017). However, the safe and efficient delivery carrier are critical barriers for successful RNAi gene delivery and therapy.…”