Background: Resistance to radiotherapy is one of the main obstacles to improving cancer prognoses. To effectively destroy cancer cells, novel radiation sensitizers are needed. Recently, several natural products have been shown to exhibit promising tumor-killing properties. However, little is known about the specific mechanisms of these natural compounds on cancer treatment. In this study, after screening a high-throughput natural product library, we identified tanshinone I (Tan I) as a potential radiation sensitizer in lung cancer cells. Methods: Lung cancer radioresistant cell lines, H358-IR and H157-IR, were first established to confirm the radioresistant phenotypes. After that, a natural product library was used to screen the potential radiation sensitizer. We further examined the inhibition functions of Tan I on radioresistant cancer cells via a series of experiments. Results: Tan I significantly inhibited cell proliferation and clone formation, consequently enhancing radiosensitivity in radioresistant lung cancer cells, H358-IR and H157-IR. Stable isotope labeling of amino acids in cell culture (SILAC)-based quantitative proteomics indicated that Tan I downregulates expression of pro-oncogenic protein phosphoribosyl pyrophosphate aminotransferase (PPAT) in both H358-IR and H157-IR cells. Further analysis of molecular docking showed that Tan I is well-docked into the active pocket of the structure of PPAT, serving as a potential PPAT inhibitor. Conclusions: Taken together, these findings suggest that inhibition of the tumor promoter PPAT by Tan I exerts marked inhibitory effects on radioresistant lung cancer cells, improving radiation efficacy.

中文翻译：

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丹参酮Ⅰ对肺癌细胞放射敏感性的影响及其机制

背景：对放射疗法的抵抗力是改善癌症预后的主要障碍之一。为了有效地破坏癌细胞，需要新型的辐射敏化剂。近来，已经显示出几种天然产物表现出有希望的杀肿瘤特性。但是，对于这些天然化合物治疗癌症的具体机制知之甚少。在这项研究中，筛选了高通量的天然产物库后，我们确定了丹参酮I（Tan I）作为肺癌细胞中潜在的辐射敏化剂。方法：首先建立肺癌放射线细胞系H358-IR和H157-IR以确定放射线型。之后，使用天然产物库筛选潜在的辐射敏化剂。我们通过一系列实验进一步研究了Tan I对放射线癌细胞的抑制功能。结果：Tan I显着抑制细胞增殖和克隆形成，因此增强了放射敏感性肺癌细胞H358-IR和H157-IR的放射敏感性。基于细胞培养（SILAC）的定量蛋白质组学中氨基酸的稳定同位素标记表明，Tan I下调了H358-IR和H157-IR细胞中促癌蛋白磷酸核糖焦磷酸氨基转移酶（PPAT）的表达。分子对接的进一步分析表明，Tan I已很好地对接到PPAT结构的活性口袋中，可作为潜在的PPAT抑制剂。结论：综上所述，