J Cancer 2020; 11(21):6348-6355. doi:10.7150/jca.44431 This issue Cite
Research Paper
1. Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, P. R. China.
2. School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, P. R. China.
3. Guangzhou Institute of Pediatrics/Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, P. R. China.
4. Institute of Immunology and School of Medicine, Shanxi Datong University, Datong 037009, P. R. China.
*These authors contributed equally to this work.
Background: The natural occurring pristimerin, a quinonemethide triterpenoid, is extracted from a variety of species of the Celastraceae and Hippocrateaceae family. This research investigated the in vitro anti-cancer potential of pristimerin on NSCLC cells NCI-H1299 and elucidated the molecular mechanism.
Methods: Cell growth inhibition by pristimerin was assessed using the MTT assay. Apoptosis was detected using the Annexin V/propidium iodide (PI) test. The colony forming assay was used to investigate the anti-proliferative effects of pristimerin. Wound healing assay and the transwell cell migration assay were utilized to determine the inhibitory effects of migration and invasion, respectively. Western blot was used to detect the protein expression, and real-time-quantitative (RT-q) PCR was used to analyze the mRNA expression.
Results: The results showed that pristimerin inhibited the proliferation of H1299 cells with an IC50 value of 2.2 ± 0.34 µM and induced apoptosis in a dose-dependent manner. The colony formation ability was reduced in a dose-dependent manner. A marked inhibition of migration and invasion against H1299 cells was observed in a dose- or time-dependent manner. Moreover, the decreased protein levels of vimentin, F-actin, integrin β1, matrix metalloproteinase (MMP2) and Snail revealed the potential inhibition of epithelial-to-mesenchymal transition (EMT). The regulated mRNA levels of integrin β1, MMP2 and Snail indicated the great potential in the treatment of NSCLC.
Conclusion: In conclusion, our study demonstrated that pristimerin suppressed NSCLC cells NCI-H1299 in vitro, exhibited potent activities of proliferation inhibition and apoptosis induction. Furthermore, the treatment of pristimerin decreased migration and invasion of H1299, which was correlated with EMT-related proteins and mRNA.
Keywords: Anti-lung cancer, NSCLC, pristimerin, anti-apoptosis, migration, invasion