Background

Oral tongue squamous cell carcinoma (OTSCC) is a popular aggressive malignancy of the oral cavity. Despite advances in OTSCC therapy, the overall 5-year survival rate is low. The tumor microenvironment resistance factors lead to chemotherapy failure, especially intratumoral hypoxia. HIF-1α, the main protein in hypoxia pathway, influences cell survival and angiogenesis. Hypoxia/HIF-1α system is a potential strategic target in cancer therapeutics. The expression of hypoxia-regulating miRNAs (hypoxamiRs; miR-210 and miR-21), regulators of HIF-1α, is high in OTSCC. Gum Arabic-encapsulated gold nanoparticles (GA-AuNPs) have been reported as promising modality in cancer treatment.

Objective

This study aimed to investigate the influence of GA-AuNPs on the hypoxia regulators in OTSCC (CAL-127 cells). GA-AuNPs cytotoxicity assessed by MTT assay; cell death mode was detected by dual DNA staining; monitoring of cellular hypoxia was followed by pimonidazole; miR-210 and miR-21 expression was assessed by qPCR; and their targets (HIF-1α and c-Myc) assayed by immunocytofluorescence and ELISA, respectively.

Results

GA-AuNPs (75–80 nm; λ_max of ~ 540 nm) reduced cell viability with IC₅₀ of 392.3 and 247.3 µg/ml after 24 h and 48 h, respectively. Cell death was mainly due to apoptosis. CAL-27 cells exhibited high hypoxia and the treatment with GA-AuNPs inhibited this hypoxia in a dose-dependent manner, as detected by pimonidazole. GA-AuNPs (30% IC₅₀) significantly reduced miR-210 and miR-21 expression. HIF-1α and c-Myc were inhibited by GA-AuNPs (30% IC₅₀, for 48 h).

Conclusion

The study findings may suggest GA-AuNPs as a promising carrier for chemotherapies to diminish intratumoral hypoxia-stimulated resistance.

中文翻译：

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阿拉伯胶包裹的金纳米颗粒调节舌鳞状细胞癌中hypoxamiRs的表达

背景

口腔舌鳞状细胞癌（OTSCC）是一种流行的口腔恶性肿瘤。尽管OTSCC治疗取得了进步，但总体5年生存率仍然很低。肿瘤微环境抵抗因子导致化疗失败，尤其是肿瘤内缺氧。缺氧途径中的主要蛋白HIF-1α影响细胞存活和血管生成。低氧/HIF-1α系统是癌症治疗中的潜在战略目标。在OTSCC中，缺氧调节性miRNA（hypoxamiRs； miR-210和miR-21）（HIF-1α的调节剂）的表达较高。据报道，阿拉伯胶封装的金纳米颗粒胶（GA-AuNPs）在癌症治疗中有望成为一种有前景的疗法。

目的

这项研究旨在调查GA-AuNPs对OTSCC（CAL-127细胞）中的缺氧调节因子的影响。通过MTT分析评估GA-AuNPs的细胞毒性；通过双重DNA染色检测细胞死亡模式；吡莫尼唑监测细胞缺氧。通过qPCR评估miR-210和miR-21的表达；分别用免疫细胞荧光法和ELISA法检测了它们的靶标（HIF-1α和c-Myc）。

结果

GA-的AuNP（75-80纳米; λ_最大〜540纳米的）降低细胞活力与IC ₅₀分别为24小时和48小时，之后的392.3和247.3微克/毫升。细胞死亡主要是由于细胞凋亡。CAL-27细胞表现出较高的缺氧状态，如吡莫硝唑检测到的那样，GA-AuNPs的处理以剂量依赖的方式抑制了该缺氧。GA-AuNPs（30％IC ₅₀）显着降低了miR-210和miR-21的表达。HIF-1α和c-Myc被GA-AuNPs抑制（30％IC ₅₀，持续48 h）。

结论

研究结果可能表明，GA-AuNPs作为有希望的化学疗法载体，可减少肿瘤内缺氧刺激的耐药性。