Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Phytomedicine. 2022 Jul;101:154109. doi: 10.1016/j.phymed.2022.154109. Epub 2022 Apr 30.
Lung cancer is one of the most common types of malignant tumor. It has one of the highest morbidity and mortality rates worldwide, and approximately 85% of cases are non-small cell lung cancer (NSCLC). Clinically, several EGFR inhibitors have been used to treat NSCLC, but resistance can develop. Studies have shown that cross talk between signal transducer and activator of transcription 3 (STAT3) and epidermal growth factor receptor (EGFR) can mediate drug resistance. Acetylshikonin has obvious antitumor effects, but the mechanism of action is still unclear.
To analyze the antitumor activity of acetylshikonin in lung cancer and clarify its molecular mechanism.
Methyl thiazolyl tetrazolium (MTT), colony formation and 5-ethynyl-2'-deoxyuridine (EDU) assays were performed to examine the effects of acetylshikonin in inhibiting the proliferation of NSCLC cells (PC-9, H1975 and A549). Scratch wound and transwell assays were used to evaluate the migration and invasion of NSCLC cells. Flow cytometry was employed to determine whether acetylshikonin could induce apoptosis. Proteome sequencing was used to identify the targets of acetylshikonin. Immunofluorescence staining and western blotting were utilized to verify the inhibition of STAT3 and EGFR phosphorylation. A xenotransplantation model was established to evaluate the efficacy of acetylshikonin in nude mice.
Our data demonstrated that acetylshikonin significantly decreased the survival rate of human NSCLC cells, increased the apoptotic rate and inhibited cell migration dose-dependently. Immunofluorescence staining and western blotting analyses revealed that acetylshikonin inhibited EGFR and STAT3 pathways. Acetylshikonin also inhibited tumor growth in a xenograft model better than inhibitors of EGFR and STAT3.
Acetylshikonin has anti-cancer effects on NSCLC cells by inhibiting EGFR and STAT3, indicating that acetylshikonin may be a new antitumor drug to treat NSCLC.
肺癌是最常见的恶性肿瘤之一。它在全球的发病率和死亡率都很高，大约 85%的病例是非小细胞肺癌（NSCLC）。临床上，已经有几种表皮生长因子受体（EGFR）抑制剂被用于治疗 NSCLC，但会产生耐药性。研究表明，信号转导和转录激活因子 3（STAT3）和表皮生长因子受体（EGFR）之间的串扰可以介导耐药性。乙酰紫草素具有明显的抗肿瘤作用，但作用机制尚不清楚。
分析乙酰紫草素在肺癌中的抗肿瘤活性，并阐明其分子机制。
采用噻唑蓝（MTT）比色法、集落形成实验和 5-乙炔基-2'-脱氧尿苷（EDU）实验检测乙酰紫草素对非小细胞肺癌细胞（PC-9、H1975 和 A549）增殖的抑制作用。划痕实验和 Transwell 实验检测乙酰紫草素对非小细胞肺癌细胞迁移和侵袭的影响。流式细胞术检测乙酰紫草素是否诱导细胞凋亡。蛋白质组学测序鉴定乙酰紫草素的作用靶点。免疫荧光染色和 Western blot 检测乙酰紫草素对 STAT3 和 EGFR 磷酸化的抑制作用。建立裸鼠异种移植模型评价乙酰紫草素的疗效。
数据表明，乙酰紫草素显著降低人非小细胞肺癌细胞的存活率，增加细胞凋亡率，并呈剂量依赖性抑制细胞迁移。免疫荧光染色和 Western blot 分析显示，乙酰紫草素抑制 EGFR 和 STAT3 通路。乙酰紫草素在异种移植模型中的抑瘤作用优于 EGFR 和 STAT3 抑制剂。
乙酰紫草素通过抑制 EGFR 和 STAT3 对 NSCLC 细胞具有抗癌作用，表明乙酰紫草素可能是一种治疗 NSCLC 的新型抗肿瘤药物。
