机构：[1]Department of Physiology, Yunnan University of Chinese Medicine, Kunming, Yunnan, China[2]College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, China[3]Department of Urology, The 1st Affiliated Hospital of Kunming Medical University, Kunming, China昆明医科大学附属第一医院[4]School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, Yunnan, China[5]Department of Anorectal, The Third Clinical Medical College, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China[6]Department of Teaching and Research of Formulas of Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, China[7]Department of Pathology, Yunnan University of Chinese Medicine, Kunming, Yunnan, China[8]Department of Oncology, Affiliated Hospital of Hebei University of Engineering, Hebei, Handan, China河北大学附属医院[9]Department of Nursing, Yunnan University of Chinese Medicine, Kunming, Yunnan, China[10]Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China[11]Yunnan Key Laboratory of Molecular Biology of Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, China[12]XingYi People’ Hospital, XingYi, Guizhou, China
Cyclin-dependent kinases (CDKs) are hyperactive in many cancers and have served as cancer therapeutic targets for decades. Palbociclib (Palb) is the first approved CDK4/6 inhibitor to treat hormone receptor (HR)-positive, HER2-negative advanced breast cancer. Acquired drug resistance is one obstacle of Palb be utilized in other cancer. CDK2 compensation of CDK4/6 loss is one of the causes that cancer cells are resistant to Palb. Hence, targeting multiple CDKs could be a novel strategy to prevent the drug resistance of cancer cells and expand the application of Palb in other cancer. In this study, we initially indicated Polyphyllin I (PPI) significantly inhibits non-small lung cancer cell (NSCLC) proliferation, promotes cell apoptosis in vitro and in vivo. Mechanistically, PPI can inhibit Rb through the p21/CDK2/Rb signaling pathway in NSCLC. A combination of PPI and Palb exerts a significant synergistic anti-cancer ability on NSCLC. Of note, PPI can reverse Palb drug resistance. Herein, we first time demonstrated PPI can disturb CDK2 function through upregulation of p21. The PPI effect on CDK2 provides a choice for a chemotherapeutic strategy for the elimination of NSCLC. Our study highlighted the clinical significance of simultaneously blocking of CDK2 and CDK4/6 for NSCLC treatment.
基金：
Yunnan Applied Basic Res of Combined Foundation of Yunnan Province Science Technology Dept; Kunming Medical University [2017FE467(-186), 2018FE001(-069], 2019FE001-064]; Zhanjiang Science and Technology Bureau Competitive Science and Technology Project [2020A100302]; Yunnan Applied Basic Res. of Combined Foundation of Yunnan Province Science & Technology Dept, Yunnan Univ. of Chinese Medicine [2018FF001-026, 2019FF002-050, 2019FF002-040, 2018FF001-016, 2018FF001-079]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [82060862, 81860881, 81960666, 81960835]; General project of Yunnan applied basic research program [2019FB118]; Guizhou Science & Technology Department [QKHJC (2017)1171]; program Innovative Research Team in Science and Technology in Yunnan Province [202005AE160004]; Yunnan Key Project [2019FA033]; [YNWR-YLXZ-2019-019]
第一作者机构：[1]Department of Physiology, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
共同第一作者：
通讯作者：
通讯机构：[7]Department of Pathology, Yunnan University of Chinese Medicine, Kunming, Yunnan, China[11]Yunnan Key Laboratory of Molecular Biology of Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, China[12]XingYi People’ Hospital, XingYi, Guizhou, China[*1]Chunrong west road 1076, Chenggong district, Kunming, China 650500
推荐引用方式(GB/T 7714)：
Shen Zhengchao,Wang Jian,Ke Kunbin,et al.Polyphyllin I, a lethal partner of Palbociclib, suppresses non-small cell lung cancer through activation of p21/CDK2/Rb pathway in vitro and in vivo[J].CELL CYCLE.2021,20(23):2494-2506.doi:10.1080/15384101.2021.1991121.
APA：
Shen, Zhengchao,Wang, Jian,Ke, Kunbin,Chen, Rong,Zuo, Aixue...&Shi, Xinan.(2021).Polyphyllin I, a lethal partner of Palbociclib, suppresses non-small cell lung cancer through activation of p21/CDK2/Rb pathway in vitro and in vivo.CELL CYCLE,20,(23)
MLA：
Shen, Zhengchao,et al."Polyphyllin I, a lethal partner of Palbociclib, suppresses non-small cell lung cancer through activation of p21/CDK2/Rb pathway in vitro and in vivo".CELL CYCLE 20..23(2021):2494-2506
