Glioblastoma (GBM) is the most common primary malignant brain tumour and lacks therapeutic options with significant effects. The aberrant activation of STAT3 is a critical factor in glioma progression via activating multiple signalling pathways that promote glioma. Among them, the antiapoptotic gene Bcl-2 could be upregulated by p-STAT3, which is an important reason for the continuous proliferation of glioma. We previously reported that bergaptol, a natural furanocoumarin widely found in citrus products, exerts antineuroinflammatory effects by inhibiting the overactivation of STAT3. Here, we aimed to evaluate whether bergaptol could promote glioma apoptosis by inhibiting the STAT3/Bcl-2 pathway. This study found that bergaptol inhibited the proliferation and migration of GBM cell lines (U87 and A172) and promoted apoptosis in vitro. We also found that bergaptol significantly inhibited the STAT3/Bcl-2 pathway in GBM cells. U87 cells were implanted intracranially into nude mice to establish a glioma model, and glioma-bearing mice were treated with bergaptol (40 mg/kg). Bergaptol treatment significantly inhibited glioma growth and prolonged the glioma-bearing mice's survival time. In addition, bergaptol administration also significantly inhibited the STAT3/Bcl-2 pathway of tumour tissue in vivo. Overall, we found that bergaptol could effectively play an antiglioma role by inhibiting STAT3/Bcl-2 pathway, suggesting the potential efficacy of bergaptol in treating glioma.

中文翻译：

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Bergaptol 通过 STAT3/Bcl-2 途径抑制神经胶质瘤细胞增殖并诱导细胞凋亡。

胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤，缺乏有效的治疗方案。 STAT3 的异常激活是神经胶质瘤进展的关键因素，通过激活多种信号通路促进神经胶质瘤。其中，抗凋亡基因Bcl-2可被p-STAT3上调，这是胶质瘤持续增殖的重要原因。我们之前报道过香柠檬醇是一种广泛存在于柑橘类产品中的天然呋喃香豆素，通过抑制 STAT3 的过度激活来发挥抗神经炎症作用。在这里，我们的目的是评估香柠檬醇是否可以通过抑制 STAT3/Bcl-2 通路来促进胶质瘤细胞凋亡。本研究发现香柠檬醇在体外抑制 GBM 细胞系（U87 和 A172）的增殖和迁移并促进细胞凋亡。我们还发现香柠檬醇显着抑制 GBM 细胞中的 STAT3/Bcl-2 通路。将U87细胞颅内植入裸鼠体内，建立胶质瘤模型，并对荷瘤小鼠给予香柠檬醇（40 mg/kg）治疗。佛手醇治疗显着抑制神经胶质瘤的生长并延长了患有神经胶质瘤的小鼠的生存时间。此外，香柠檬醇给药还显着抑制体内肿瘤组织的STAT3/Bcl-2通路。总的来说，我们发现香柠檬醇可以通过抑制STAT3/Bcl-2通路有效发挥抗神经胶质瘤作用，这表明香柠檬醇在治疗神经胶质瘤中具有潜在功效。