Ye Yong, Zhang Bo, Liang Qiuyun, Wang Dandan, Bai Facheng, Li Yuanhong, Wei Lizhi, Li Lilan, Huang Huixue, Tang Yunxia
Pharmacy College, Guangxi Medical University, Nanning, China.
Scientific Research Center, Guilin Medical University, Guilin, China.
Front Oncol. 2022 Aug 9;12:946758. doi: 10.3389/fonc.2022.946758. eCollection 2022.
Breast cancer (BC) is one of the most common malignant tumors in women and poses a serious threat to their health. Compound Kushen injection (CKI) has shown therapeutic effects on a variety of cancers, including BC, and it can significantly improve the lives of patients. However, the underlying mechanism remains unclear and needs to be fully elucidated.
The active constituents of CKI were identified through a literature review, and the anti-BC targets of CKI were determined using multiple databases and a ChIP data analysis. Subsequently, the target was analyzed on the DAVID database through GO and KEGG to identify the key pathway that CKI affects to exhibit anti-BC activity. In addition, MCF-7 and MDA-MB-231 cells were treated with CKI for 24 and 48 hours at five concentrations, and the effects of CKI on cell proliferation and apoptosis were measured using MTT and annexin V/propidium iodide staining assays, respectively. The genes and protein identified to be involved in this pathway were verified using real-time quantitative PCR (qPCR) and western blot(WB) in BC cells.
Twelve CKI anti-BC targets were obtained by a comprehensive analysis of the targets collected in the databases and results from the ChIP analysis. Bioinformatics analysis was performed for 12 targets. KEGG analysis showed that the 12 targets were mainly related to the VEGF, ErbB, and TNF signaling pathways. We focused our study on the VEGF signaling pathway as the -value for the VEGF signaling pathway was the lowest among the three pathways. experiments showed that CKI significantly inhibited the proliferation of BC cells and induced apoptosis. Furthermore, qPCR and WB experiments showed that the expression of VEGF signaling pathway genes PIK3CA and NOS3 were significantly increased meanwhile SRC was significantly decreased after CKI intervention.
CKI significantly inhibited the proliferation of BC cells and induced apoptosis. The main mechanism for the anti-BC effect of CKI may be that it regulates the VEGF signaling pathway by increasing the expression of PIK3CA, SRC, and NOS3. Macrozamin and lamprolobine may be the main active components of CKI against BC.
乳腺癌（BC）是女性最常见的恶性肿瘤之一，对她们的健康构成严重威胁。复方苦参注射液（CKI）已显示出对包括BC在内的多种癌症具有治疗作用，并且可以显著改善患者的生活。然而，其潜在机制仍不清楚，需要充分阐明。
通过文献综述确定CKI的活性成分，并使用多个数据库和ChIP数据分析确定CKI的抗BC靶点。随后，通过DAVID数据库上的GO和KEGG对该靶点进行分析，以确定CKI发挥抗BC活性所影响的关键途径。此外，用五种浓度的CKI处理MCF-7和MDA-MB-231细胞24和48小时，分别使用MTT和膜联蛋白V/碘化丙啶染色试验检测CKI对细胞增殖和凋亡的影响。在BC细胞中使用实时定量PCR（qPCR）和蛋白质印迹（WB）验证鉴定出参与该途径的基因和蛋白质。
通过对数据库中收集的靶点和ChIP分析结果进行综合分析，获得了12个CKI抗BC靶点。对12个靶点进行了生物信息学分析。KEGG分析表明，这12个靶点主要与VEGF、ErbB和TNF信号通路相关。由于VEGF信号通路的 -值在这三个通路中最低，我们将研究重点放在VEGF信号通路上。实验表明，CKI显著抑制BC细胞的增殖并诱导凋亡。此外，qPCR和WB实验表明，CKI干预后，VEGF信号通路基因PIK3CA和NOS3的表达显著增加，而SRC显著降低。
CKI显著抑制BC细胞的增殖并诱导凋亡。CKI抗BC作用的主要机制可能是通过增加PIK3CA、SRC和NOS3的表达来调节VEGF信号通路。苦豆碱和氧化苦参碱可能是CKI抗BC的主要活性成分。
