Dauricine Inhibits Non-small Cell Lung Cancer Development by Regulating PTEN/AKT/mTOR and Ras/MEK1/2/ERK1/2 Pathways in a FLT4-dependent Manner

被引：3
作者：
Liang, Jinna [1 ,2 ]
Lei, Panpan [1 ,2 ]
Su, Xinyue [1 ,2 ]
Gao, Jiapan [1 ,2 ]
Ren, Bingxi [1 ,2 ]
Zhang, Yuxiu [1 ,2 ]
Ma, Xiaoyu [1 ,2 ]
Ma, Weina [1 ,2 ]
机构：
[1] Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Pharm, 76 Yanta West St 54, Xian 710061, Shaanxi, Peoples R China
[2] State Key Lab Shaanxi Nat Med Res & Engn, Xian 710061, Peoples R China
来源：
CURRENT CANCER DRUG TARGETS | 2024年 / 24卷 / 11期
关键词：
NSCLC; dauricine; VEGFR3; FLT4; cell growth; cell migration; ENDOTHELIAL GROWTH-FACTOR; VEGF-C; ANTITUMOR-ACTIVITY; AXIS; PROLIFERATION; PROGRESSION; METASTASIS; APOPTOSIS;
D O I：
10.2174/0115680096282997240101192452
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Objective Non-small cell lung cancer (NSCLC) is still a solid tumor with high malignancy and poor prognosis. Vascular endothelial growth factor receptor 3 (FLT4, VEGFR3) is overexpressed in NSCLC cells, making it a potential target for NSCLC treatment. In this study, we aimed to explore the anti-cancer effects of dauricine on NSCLC cells and its mechanism targeting FLT4.Methods We found that dauricine inhibited the growth of NCI-H1299 cells by blocking the cycle in the G2/M phase through flow cytometry analysis. In addition, dauricine also inhibited the migration of NCI-H1299 cells by wound healing assay and transwell migration assay. More importantly, our empirical analysis found the anti-cancer effect of dauricine on NCI-H1299 cells and the protein level of FLT4 had a distinctly positive correlation, and this effect was weakened after FLT4 knockdown.Results It is suggested that dauricine suppressed the growth and migration of NCI-H1299 cells by targeting FLT4. Furthermore, dauricine inhibited FLT4 downstream pathways, such as PTEN/AKT/mTOR and Ras/MEK1/2/ERK1/2, thereby regulating cell migration-related molecule MMP3 and cell cycle-related molecules (CDK1, pCDK1-T161, and cyclin B1).Conclusion Dauricine may be a promising FLT4 inhibitor for the treatment of NSCLC.
引用
收藏
页码：1157 / 1168
页数：12
相关论文
共 40 条
[1]   VEGFR3 suppression through miR-1236 inhibits proliferation and induces apoptosis in ovarian cancer via ERK1/2 and AKT signaling pathways [J].
Babaei, Zeinab ;
Panjehpour, Mojtaba ;
Ghorbanhosseini, Seyedeh Sara ;
Parsian, Hadi ;
Khademi, Mahsa ;
Aghaei, Mahmoud .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2023, 124 (05) :674-686
[2]   Apigenin inhibits renal cell carcinoma cell proliferation through G2/M phase cell cycle arrest [J].
Bao, Yuhang ;
Wu, Xiuxian ;
Jin, Xinghua ;
Kanematsu, Akihiro ;
Nojima, Michio ;
Kakehi, Yoshiyuki ;
Yamamoto, Shingo .
ONCOLOGY REPORTS, 2022, 47 (03)
[3]  
Bray F, 2018, CA-CANCER J CLIN, V68, P1, DOI [DOI 10.3322/CANJCLIN.49.1.33, 10.3322/caac.21492, DOI 10.3322/caac.20115]
[4]   Deoxyelephantopin from Elephantopus scaber Inhibits HCT116 Human Colorectal Carcinoma Cell Growth through Apoptosis and Cell Cycle Arrest [J].
Chan, Chim Kei ;
Chan, Gomathi ;
Awang, Khalijah ;
Kadir, Habsah Abdul .
MOLECULES, 2016, 21 (03)
[5]   Phytochemicals targeting NF-κB signaling: Potential anti-cancer interventions [J].
Chauhan, Akansha ;
Ul Islam, Asim ;
Prakash, Hridayesh ;
Singh, Sandhya .
JOURNAL OF PHARMACEUTICAL ANALYSIS, 2022, 12 (03) :394-405
[6]   MiR-519d suppresses breast cancer tumorigenesis and metastasis via targeting MMP3 [J].
Chu, Chengling ;
Liu, Xin ;
Bai, Xue ;
Zhao, Tong ;
Wang, Mengxue ;
Xu, Ranchen ;
Li, Mingqi ;
Hu, Yingying ;
Li, Weihua ;
Yang, Lida ;
Qin, Youyou ;
Yang, Meng ;
Yan, Chaoqi ;
Zhang, Yong .
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2018, 14 (02) :228-236
[7]   New approaches to molecular cancer therapeutics [J].
Collins, Ian ;
Workman, Paul .
NATURE CHEMICAL BIOLOGY, 2006, 2 (12) :689-700
[8]   Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy [J].
Dias, S ;
Choy, M ;
Alitalo, K ;
Rafii, S .
BLOOD, 2002, 99 (06) :2179-2184
[9]   VEGF-targeted therapy: mechanisms of anti-tumour activity [J].
Ellis, Lee M. ;
Hicklin, Daniel J. .
NATURE REVIEWS CANCER, 2008, 8 (08) :579-591
[10]   RNAi-mediated silencing of VEGF-C inhibits non-small cell lung cancer progression by simultaneously down-regulating the CXCR4, CCR7, VEGFR-2 and VEGFR-3-dependent axes-induced ERK, p38 and AKT signalling pathways [J].
Feng, Yukuan ;
Hu, Jing ;
Ma, Jing ;
Feng, Kejian ;
Zhang, Xiaoli ;
Yang, Shucai ;
Wang, Wei ;
Zhang, Jianguo ;
Zhang, Yafang .
EUROPEAN JOURNAL OF CANCER, 2011, 47 (15) :2353-2363
1234