Ligustroflavone mediates the resistance of non-small cell lung cancer to osimertinib by arresting G1/S phase
10.16438/j.0513-4870.2023-0382
- VernacularTitle:女贞苷通过阻滞G1/S期抑制非小细胞肺癌奥西替尼耐药细胞增殖
- Author:
Tian LI
1
;
Ting WANG
2
;
Bao-juan XING
2
;
Zi-heng HE
2
;
Jiao CHEN
2
;
Xue-ting CAI
2
;
He CUI
1
;
Peng CAO
3
Author Information
1. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
2. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China
3. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China
- Publication Type:Research Article
- Keywords:
non-small cell lung cancer;
rug resistance;
osimertinib;
ligustroflavone;
cyclin-dependent kinase 6
- From:
Acta Pharmaceutica Sinica
2023;58(11):3349-3353
- CountryChina
- Language:Chinese
-
Abstract:
Natural products are an important source for the development of antitumor lead compounds, but the pharmacological effects and regulatory mechanisms of natural products in osimertinib resistance in non-small cell lung cancer (NSCLC) are not well understood. The natural product ligustroflavone was used as the research object to analyze its efficacy in osimertinib-resistant NSCLC cells by cell proliferation assay and cell cycle detection. The potential targets of ligustroflavone in osimertinib-resistant NSCLC cells were screened by public databases and bioinformatics, molecular docking and microscale thermophoresis were used to identify the interaction between privet and target molecules. Western blot was used to detect the effect of privet on the target molecules and their downstream pathways. Ligustroflavone reduced the proliferation of osimertinib-resistant NSCLC cells, and could arrest the cell cycle. Cyclin-dependent kinase 6 (CDK6) was the potential target of ligustroflavone in osimertinib-resistant NSCLC cells. Ligustroflavone inhibited the activation of CDK6-Rb axis. Together, ligustroflavone could regulate osimertinib resistance in NSCLC cells by binding cell cyclin-related molecules. This study provides a theoretical basis for the targeted drug resistance of NSCLC with natural products, and also provides a new idea for the development of clinical drug combination.
