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首页> 外文期刊>RSC Advances >Astragali radix total flavonoid synergizes cisplatin to inhibit proliferation and enhances the chemosensitivity of laryngeal squamous cell carcinoma
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Astragali radix total flavonoid synergizes cisplatin to inhibit proliferation and enhances the chemosensitivity of laryngeal squamous cell carcinoma

机译：黄芪总黄酮协同顺铂抑制增殖并增强喉鳞癌的化学敏感性

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Laryngeal squamous cell carcinoma (LSCC) is the most common head and neck cancer. Astragali radix extracts play crucial roles in the regulation of cancer progression. However, the role of Astragali radix extracts in LSCC and the related mechanisms remains unclear. Here, we evaluated the inhibitory effects of the combined use of Astragali radix total flavonoid (TFA) and cisplatin (CDDP) on an LSCC mouse model by pharmacodynamics. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed to define the prototype of TFA in vivo . The potential drug targets were identified through the integrative analysis of LSCC microarrays, RNA sequencing data and the main bioactive component of TFA. Furthermore, a protein–protein interaction network, compound–target network and target–pathway network were constructed based on the prototype and potential drug targets to identify the main targets and pathways. Animal experiments showed that TFA has significant synergistic antitumor activity with cisplatin and attenuates the nephrotoxicity caused by CDDP chemotherapy, improving the survival of LSCC-bearing mice. Using UPLC-MS/MS, we identified 8 constituents of TFA in experimental mice serum: formononetin, ononin, calycosin, calycosin-7- O -β-D-glucoside, 7,2′-dihydroxy-3′,4′-dimethoxyisoflavan, 7,2′-dihydroxy-3′,4′-dimethoxyisoflavaneglucoside, 3-hydroxy-9,10-dimethoxypterocarpan and 9,10-dimethoxyptercarpan-3- O -β- D -glucoside. Integrative analysis predicted 19 target genes for TFA constituents, and the target genes were mainly involved in the EGFR-related cancer signaling, metabolism and oxidative stress. Collectively, these findings highlight the role of TFA in the regulation of LSCC and provide potential targets for a high-efficiency and low-toxicity therapeutic strategy of LSCC.
机译：喉鳞状细胞癌（LSCC）是最常见的头颈癌。黄芪提取物在调节癌症进展中起关键作用。然而，黄芪提取物在LSCC中的作用及其相关机制仍不清楚。在这里，我们通过药效学评估了黄芪总黄酮（TFA）和顺铂（CDDP）联合使用对LSCC小鼠模型的抑制作用。采用超高效液相色谱串联质谱（UPLC-MS / MS）定义了体内TFA的原型。通过对LSCC芯片，RNA测序数据和TFA主要生物活性成分的综合分析，确定了潜在的药物靶标。此外，在原型和潜在药物靶标的基础上，构建了蛋白质-蛋白相互作用网络，化合物-靶标网络和靶标-通路网络，以识别主要靶标和途径。动物实验表明，TFA与顺铂具有显着的协同抗肿瘤活性，并能减轻CDDP化疗引起的肾毒性，从而改善LSCC荷瘤小鼠的存活率。使用UPLC-MS / MS，我们在实验小鼠血清中鉴定了TFA的8种成分：formononetin，ononin，calycosin，calycosin-7-O-β-D-葡萄糖苷，7,2'-二羟基-3'，4'-二甲氧基异黄酮，7，2′-二羟基-3′，4′-二甲氧基异黄酮葡萄糖苷，3-羟基-9，10-二甲氧基翼果聚糖和9，10-二甲氧基翼果聚糖-3-O-β-D-葡糖苷。整合分析预测了19种TFA成分的靶基因，这些靶基因主要参与EGFR相关的癌症信号，代谢和氧化应激。这些发现共同强调了TFA在LSCC调节中的作用，并为LSCC的高效率和低毒性治疗策略提供了潜在的靶标。

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