Analysis of Molecular Mechanism of YiqiChutan Formula Regulating DLL4-Notch Signaling to Inhibit Angiogenesis in Lung Cancer
Authors: Zhe Sun
Yao Chen
Xinying Xie
Jiayin Li
Linzhu Zhai
Jiamin Luo
Jing Zhang
Sisi Wang
Rui Han
Yang Cao
Qiuye Yang
Lizhu Lin
Jing Li
Journal: BioMed Research International (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: YiqiChutan formula; lung cancer; angiogenesis; DLL4-Notch signaling; tumor growth
Affiliations: Cancer Center, The First Affiliated Hospital to Guangzhou University of Chinese Medicine, Guangzhou 510405, China., Department of Oncology, The First Affiliated Hospital to Hunan University of Chinese Medicine, Changsha 410000, China., Department of General, The First Affiliated Hospital to Guangzhou University of Chinese Medicine, Guangzhou 510405, China., The First Affiliated Hospital to Guangzhou University of Chinese Medicine, Guangzhou 510405, China., Department of Medical Technologic, The First Affiliated Hospital to Guangzhou University of Chinese Medicine, Guangzhou 510405, China.

Abstract:  In order to explore the specific mechanism of YiqiChutan formula (YQCTF) in inhibiting the angiogenesis of lung cancer and its relationship with delta-like ligand 4- (DLL4-) Notch signaling, 30 healthy BALB/c-nu/nu rats were selected and divided into three groups: A549 group (implanted with lung adenocarcinoma cell line A549), NCI-H460 group (implanted with human lung large-cell carcinoma cell line NCI-H460), and NCI-H446 group (implanted with human lung small cell carcinoma cell line NCI-H446) for constructing lung cancer transplanted tumor models. After modeling, the group treated with normal saline was taken as control group, 200 mg/kg of YQCTF was adopted for intervention, and the tumor volume and growth inhibition rate were compared with the vascular targeted inhibitor Sorafenib. HE staining, CD31 fluorescent antibody staining, and microelectron microscopy were adopted to observe the neovascular endothelial cells of the transplanted tumor. The expression of VEGF, HIF-1α, DLL4, and Notch-1 in the transplanted tumors in each group was detected by Western blot and RT-PCR at the protein level or mRNA level. Compared with the control group, the YQCTF-treated group had obvious inhibitory effect on lung cancer transplanted tumor and lung cancer angiogenesis. In the YQCTF-treated group, the density of angiogenesis decreased significantly and the vascular lumen structure also decreased, and the expression levels of VEGF, HIF-1α, DLL4, and Notch-1 in the YQCTF-treated group were all lower than those in the control group. YQCTF could inhibit the growth of lung cancer transplanted tumor through antiangiogenesis, and it could also reduce the amount of angiogenesis in lung cancer transplanted tumor. In addition, the generation of lumen structure was also hindered, which was realized through the VEGF signaling pathway and DLL4-Notch signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 2 3B 3C: looking at the tumour sizes in photo 2 they did not reflect at all the changes represented by bar graphs in photo 3B and 3C. ![file] FIgure 4: it seems that the same photo has bee used for the different conditions represented. ![file] , 
 In addition to the image overlaps illustrated above within Figure 4, with which I agree, there also seems to be overlap between Figure 4 and Figure 2g in an earlier unrelated paper: Cell Death and Disease (2017), doi: 10.1038 cddis.2017.18. *** ![file] *** Acknowledgments: This study was supported by the General program of National Natural Science Foundation of China (No. 81873147), the Scientific research project of traditional Chinese medicine in Guangdong Province (Nos. 20191106 and 20201113), and the Youth Research Fund Project of u201cinnovation and strengthening hospitalu201d in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (No. 2019QN02). , 
 There seem to be some unexpected similarities between Western blot panels in Figure 7. The most notable is marked in green. *** ![file] ,