参芪扶正注射液通过调节Bax/Bcl-2信号通路抑制非小细胞肺癌细胞生长。
Shenqi Fuzheng injection hinders non-small cell lung cancer cell growth by regulating the Bax/Bcl-2 signaling pathway.
作者信息
Li Siqi, Ma Tianyu, Li Gege, Cheng Xu, Wen Tao, Wang Yuxuan, Zhang Hongtao, Liu Zhidong
机构信息
No. 2 Department of Thoracic Surgery, Beijing Chest Hospital/Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical University, Beijing, China.
Department of Thoracic Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
出版信息
Discov Oncol. 2024 May 29;15(1):195. doi: 10.1007/s12672-024-01029-6.
INTRODUCTION
Lung cancer (LC) is the most common solid tumor and is currently considered the primary cause of cancer-related deaths worldwide. In clinical efficacy studies, it was not difficult to find that the combination of SFI and chemotherapy could improve the general condition of patients, reduce the side effects of chemotherapy drugs, and have a cooperative antitumor effect in NSCLC patients. However, whether SFI can be used as a novel antitumor drug is still unknown.
METHODS
First, meta-analysis aimed to explore the efficacy of SFI in NSCLC patients, and SFI was identified by ultra-performance liquid chromatography‒mass spectrometry (UPLC‒MS). Cell proliferation, migration, and invasion were explored by Cell Counting Kit-8 (CCK-8), scratch healing, and Transwell assays, respectively. Cell cycle and apoptosis assays were performed by flow cytometry. Transcriptome sequencing analysis was performed in four NSCLC cell lines. Differential expression analysis was used to identify potential targets. Apoptosis-related protein levels were detected by Western blotting assays. The effects of SFI in NSCLC were further investigated by mouse xenografts.
RESULTS
SFI could markedly improve the chemotherapy efficacy of NSCLC patients. The main active ingredients include flavonoids and terpenoids, which can effectively exert antitumor effects. SFI could not only inhibit tumor cell proliferation and cell migration/invasion but also regulate the cell cycle and promote tumor cell apoptosis. In NSCLC, SFI could enhance the transcription level of the CHOP gene, thereby upregulating the expression of the proapoptotic proteins Bax and caspase 3, and inhibiting the expression of the antiapoptotic protein Bcl-2. SFI hindered the growth of mouse NSCLC xenografts in vivo.
CONCLUSIONS
SFI hindered tumor progression and might promote apoptosis by increasing the expression of Bax, caspase 3 and decreasing the level of Bcl-2 in NSCLC.
引言
肺癌（LC）是最常见的实体瘤，目前被认为是全球癌症相关死亡的主要原因。在临床疗效研究中，不难发现参附注射液（SFI）与化疗联合使用可改善患者的一般状况，降低化疗药物的副作用，并对非小细胞肺癌（NSCLC）患者产生协同抗肿瘤作用。然而，SFI是否可作为一种新型抗肿瘤药物仍不清楚。
方法
首先，进行荟萃分析以探讨SFI对NSCLC患者的疗效，并用超高效液相色谱-质谱联用仪（UPLC-MS）鉴定SFI。分别通过细胞计数试剂盒-8（CCK-8）、划痕愈合试验和Transwell试验探讨细胞增殖、迁移和侵袭情况。通过流式细胞术进行细胞周期和凋亡检测。对四种NSCLC细胞系进行转录组测序分析。使用差异表达分析来鉴定潜在靶点。通过蛋白质免疫印迹法检测凋亡相关蛋白水平。通过小鼠异种移植进一步研究SFI在NSCLC中的作用。
结果
SFI可显著提高NSCLC患者的化疗疗效。其主要活性成分包括黄酮类和萜类化合物，可有效发挥抗肿瘤作用。SFI不仅能抑制肿瘤细胞增殖和细胞迁移/侵袭，还能调节细胞周期并促进肿瘤细胞凋亡。在NSCLC中，SFI可增强CHOP基因的转录水平，从而上调促凋亡蛋白Bax和半胱天冬酶3的表达，并抑制抗凋亡蛋白Bcl-2的表达。SFI在体内可抑制小鼠NSCLC异种移植瘤的生长。
结论
SFI通过增加NSCLC中Bax、半胱天冬酶3的表达并降低Bcl-2水平来阻碍肿瘤进展，并可能促进细胞凋亡。
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