Synergistic effect of microRNA and albumin-bound nanoparticles for inhibition of glioblastoma cancer cell proliferation

The functional significance of upregulation miR-34a in combination with albumin-bound paclitaxel nanoparticles in U251 glioblastoma cell line has been evaluated. The MTT assay determined that miR-34a and albumin-bound paclitaxel nanoparticles can reduce cell viability, but the combination of both factors has a stronger effect on cell viability. The application of qRT-PCR has demonstrated that the transduction of miR-34a could lead to exogenous upregulation of miR-34a level and downregulation of SURVIVIN. Moreover, treatment of U251 cells with miR-34a and nanoparticles together considerably inhibit SURVIVIN expression compared to miR-34a and nanoparticles alone. Flow cytometry showed that upon miR-34a overexpression cell cycle arrested in G1 phase, while treatment with nanoparticles increased the cell population in G2 phase. Upregulation of miR-34a along with treatment with nanoparticles elevated the number of cells arrested in G1/ G2 phases of the cell cycle. Expression of miR-34a with albumin-bound paclitaxel nanoparticles reduced cell viability, downregulated SURVIVIN and enhanced cell cycle arrest in G1/G2 phases. Thus, the upregulation of miR-34a with these nanoparticles are potential candidates therapeutic for glioblastoma cancer.

本研究评估了在U251胶质母细胞瘤细胞系中，上调微小RNA-34a（miR-34a）联合白蛋白结合型紫杉醇纳米颗粒（albumin-bound paclitaxel nanoparticles）的功能意义。通过MTT实验检测发现，miR-34a与白蛋白结合型紫杉醇纳米颗粒均可降低细胞活力，且二者联合使用对细胞活力的抑制效果更强。实时荧光定量聚合酶链反应（qRT-PCR）结果证实，转染miR-34a可导致miR-34a水平的外源性上调，并下调存活素（SURVIVIN）的表达。此外，与单独使用miR-34a或纳米颗粒相比，二者联合处理U251细胞可显著抑制SURVIVIN的表达。流式细胞术（Flow cytometry）结果显示，miR-34a过表达时细胞周期阻滞于G1期，而纳米颗粒处理则使G2期细胞比例升高。上调miR-34a联合纳米颗粒处理，可使阻滞于细胞周期G1/G2期的细胞数量进一步增加。miR-34a联合白蛋白结合型紫杉醇纳米颗粒处理，可降低细胞活力、下调SURVIVIN表达，并增强细胞周期G1/G2期阻滞。综上，上调miR-34a联合此类纳米颗粒有望成为胶质母细胞瘤的潜在治疗候选方案。