Objective: Ganoderic acid A can inhibit the proliferation and promotes the apoptosis of cancer cells. Surprisingly, the molecular mechanisms underlying the anti-cancer effects of ganoderic acid A still remain poorly defined. Ganoderic acid A derivative (GaAD19) is an effective ingredient obtained by structural modification of ganoderic acid A. The purpose of this study was to evaluate the anti-proliferation effect of GaAD19 on cervical cancer cells. Methods: Through the HeLa cervical cancer cell model, the drug target of GaAD19 was predicted using the SwissTargetPrediction database and molecular docking. Subsequently, computer analysis results were verified by a series of molecular biology experiments, such as flow cytometry, Western blot, immunocytochemical staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), quantitative real time polymerase chain reaction (qPCR), and so on. Then, pathway agonists and inhibitors were used to investigate the mechanism of GaAD19. Finally, the mouse model of cervical cancer was established to evaluate the inhibitory effect of GaAD19 on tumor growth in U14 cervical cancer mice. Results: GaAD19 induced apoptosis and inhibited the growth of tumors. It also blocked the transition from the G1 to the S phase of the cell cycle. However, in the presence of a c-Jun N-terminal kinase (JNK)agonist, the effects of GaAD19 on the proliferation, apoptosis, and cell cycle transition of cancer cells were suppressed. Conclusion: This study showed that GaAD19 can play an anti-cervical cancer role by inhibiting the JNK signaling pathway. These results will be helpful in further exploring the mechanism of GaAD19 in the treatment of cervical cancer.
关键词:
抗肿瘤;细胞凋亡;子宫颈癌;灵芝酸A衍生物;JNK信号通路
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Project Supported:
This study was supported by CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2021-I2M-1-031) and National Key Research and Development Plan Program (No. 2019YFC1710504).
