Abstract

Baicalin plays important roles in different types of cancer. A previous report showed that baicalin attenuates cisplatin resistance in lung cancer. However, its mechanism remains unclear. In this study, we investigated the effect and mechanism of baicalin on DNA repair and sensitivity of lung cancer cells to cisplatin. A549 and A549/DPP cells were treated with baicalin and cisplatin. A549/DPP cells were transfected with XRCC1 and siXRCC1. Cell viability and DNA damage were detected by MTT and comet assay. Apoptosis rate and cell cycle were detected by flow cytometry assay. The expressions of Bax, Bcl-2, and Cyclin D1 were detected by western blot. XRCC1 expression was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. Baicalin and cisplatin decreased cell viability in A549 and A549/DPP cells in dose-dependent manner. Baicalin enhanced the effect of cisplatin on promoting apoptosis, arresting cell on S stage and triggering DNA damage accompanied with the upregulation of Bcl-2-associated X protein (Bax) and downregulation of B-cell lymphoma 2 (Bcl-2) and Cyclin D1 in A549/DPP cells. Moreover, baicalin promoted the inhibitory effect of cisplatin on XRCC1 expression in A549 and A549/DPP cells. However, the synthetic effects of baicalin and cisplatin on A549/DPP cells were partially inhibited by XRCC1 overexpression and promoted by XRCC1 knockdown. This study demonstrates that baicalin interferes with XRCC1-mediated cellar DNA repair to sensitize lung cancer cells to cisplatin.

摘要

黄芩苷在不同类型的癌症中起重要作用。先前的一份报告显示，黄芩苷可减轻肺癌的顺铂耐药性。然而，其机制仍不清楚。在这项研究中，我们研究了黄芩苷对 DNA 修复和肺癌细胞对顺铂敏感性的影响和机制。A549 和 A549/DPP 细胞用黄芩苷和顺铂处理。用 XRCC1 和 siXRCC1 转染 A549/DPP 细胞。通过MTT和彗星试验检测细胞活力和DNA损伤。流式细胞仪检测细胞凋亡率和细胞周期。Western blot检测Bax、Bcl-2和Cyclin D1的表达。通过逆转录定量聚合酶链反应（RT-qPCR）和蛋白质印迹检测XRCC1的表达。黄芩苷和顺铂以剂量依赖性方式降低 A549 和 A549/DPP 细胞的细胞活力。黄芩苷增强顺铂促进细胞凋亡、将细胞阻滞在 S 期和触发 DNA 损伤的作用，同时上调 Bcl-2 相关 X 蛋白 (Bax) 和下调 B 细胞淋巴瘤 2 (Bcl-2) 和 Cyclin D1在 A549/DPP 细胞中。此外，黄芩苷促进顺铂对 A549 和 A549/DPP 细胞中 XRCC1 表达的抑制作用。然而，黄芩苷和顺铂对 A549/DPP 细胞的合成作用受到 XRCC1 过表达的部分抑制和 XRCC1 敲低的促进。这项研究表明，黄芩苷干扰 XRCC1 介导的细胞 DNA 修复，使肺癌细胞对顺铂敏感。在 A549/DPP 细胞中，将细胞阻滞在 S 期并引发 DNA 损伤，同时伴随 Bcl-2 相关 X 蛋白 (Bax) 的上调和 B 细胞淋巴瘤 2 (Bcl-2) 和 Cyclin D1 的下调。此外，黄芩苷促进顺铂对 A549 和 A549/DPP 细胞中 XRCC1 表达的抑制作用。然而，黄芩苷和顺铂对 A549/DPP 细胞的合成作用受到 XRCC1 过表达的部分抑制和 XRCC1 敲低的促进。这项研究表明，黄芩苷干扰 XRCC1 介导的细胞 DNA 修复，使肺癌细胞对顺铂敏感。在 A549/DPP 细胞中，将细胞阻滞在 S 期并引发 DNA 损伤，同时伴随 Bcl-2 相关 X 蛋白 (Bax) 的上调和 B 细胞淋巴瘤 2 (Bcl-2) 和 Cyclin D1 的下调。此外，黄芩苷促进顺铂对 A549 和 A549/DPP 细胞中 XRCC1 表达的抑制作用。然而，黄芩苷和顺铂对 A549/DPP 细胞的合成作用受到 XRCC1 过表达的部分抑制和 XRCC1 敲低的促进。这项研究表明，黄芩苷干扰 XRCC1 介导的细胞 DNA 修复，使肺癌细胞对顺铂敏感。黄芩苷促进顺铂对 A549 和 A549/DPP 细胞 XRCC1 表达的抑制作用。然而，黄芩苷和顺铂对 A549/DPP 细胞的合成作用受到 XRCC1 过表达的部分抑制和 XRCC1 敲低的促进。这项研究表明，黄芩苷干扰 XRCC1 介导的细胞 DNA 修复，使肺癌细胞对顺铂敏感。黄芩苷促进顺铂对 A549 和 A549/DPP 细胞 XRCC1 表达的抑制作用。然而，黄芩苷和顺铂对 A549/DPP 细胞的合成作用受到 XRCC1 过表达的部分抑制和 XRCC1 敲低的促进。这项研究表明，黄芩苷干扰 XRCC1 介导的细胞 DNA 修复，使肺癌细胞对顺铂敏感。