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Antitumor effects of Andrographis via ferroptosis-associated genes in gastric cancer

机译:穿心莲通过铁死亡相关基因在胃癌中的抗肿瘤作用

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摘要

The overall prognosis of advanced/metastatic gastric cancer (GC) remains poor despite the development of pharmacotherapy. Therefore, other treatment options, such as complementary and alternative medicine, should be considered to overcome this aggressive malignancy. Andrographis, which is a generally unharmful botanical compound, has gained increasing interest for its anticancer effects in multiple malignancies via the regulation of cancer progression-associated signaling pathways. In the present study, a series of in vitro experiments (cell proliferation, colony formation and apop-tosis assays) was designed to elucidate the antitumor potential and mechanism of Andrographis in GC cells. The present study demonstrated that Andrographis exerted antitumor effects in GC cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Furthermore, it was demonstrated that the expression levels of the ferroptosis-associated genes heme oxygenase-1, glutamate-cysteine ligase catalytic and glutamate-cysteine ligase modifier were significantly upregu-lated after Andrographis treatment in both GC cell lines in reverse transcription-quantitative PCR experiments (P<0.05); this finding was further confirmed by immunoblotting assays (P<0.05). In conclusion, to the best of our knowledge, the present study was the first to demonstrate that Andrographis possessed antitumor properties by altering the expression levels of ferroptosis-associated genes, thereby providing novel insights into the potential of Andrographis as an adjunctive treatment option for patients with metastatic GC.
机译:尽管药物治疗有所发展,但晚期/转移性胃癌 (GC) 的总体预后仍然较差。因此,应考虑其他治疗方案,例如补充和替代医学,以克服这种侵袭性恶性肿瘤。穿心莲是一种通常无害的植物化合物,通过调节癌症进展相关的信号通路,其在多种恶性肿瘤中的抗癌作用越来越受到关注。本研究通过一系列体外实验(细胞增殖、集落形成和细胞凋亡试验)来阐明穿心莲在GC细胞中的抗肿瘤潜力和机制。本研究表明,穿心莲通过抑制增殖、减少集落形成和增强细胞凋亡活性在GC细胞系(MKN74和NUGC4)中发挥抗肿瘤作用。逆转录定量PCR实验显示,穿心莲处理后,铁死亡相关基因血红素加氧酶-1、谷氨酸-半胱氨酸连接酶催化和谷氨酸-半胱氨酸连接酶修饰剂的表达水平均显著上调(P<0.05);免疫印迹试验进一步证实了这一发现(P<0.05)。总之,据我们所知,本研究首次证明穿心莲通过改变铁死亡相关基因的表达水平具有抗肿瘤特性,从而为穿心莲作为转移性胃食镜患者辅助治疗选择的潜力提供了新的见解。

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