Mobile website
Archive > Volume 31 Issue 4 > 2024,31(4):333-341. DOI:10.3872/j.issn.1007-385X.2024.04.003 Prev Next
Basic Research
Effects of α-hederin alone or in combination with cisplatin on the proliferation and apoptosis of non-small cell lung cancer cells based on EGFR/AKT and JAK2/STAT3 pathways
- Article
- Figures
- Metrics
- Preview PDF
- Reference
- Related
- Cited by
- Materials
Abstract:
Objective: To explore the targets and potential mechanism of α-hederin (α-Hed) inducing cell apoptosis on non-small cell lung cancer (NSCLC), and to clarify the effects of α-Hed in combination with cisplatin (DDP) on the expression of target proteins. Methods: The viability of NSCLC cells (A549, H1299 and PC-9 cells) treated with different concentrations of α-Hed was detected by CCK-8 method.The apoptosis rate was determined by flow cytometry with Annexin Ⅴ-FITC/PI staining. The expressions of cleaved caspase-3 (C-caspase-3)and Bcl-2 proteins were detected by Western blot. The potential targets of α-Hed were screened by network pharmacology, and their binding effect was analyzed by molecular docking method. Besides, Western blot was applied to detect target protein expression. The suppressive effect of α-Hed in combination with DDP on NSCLC cells was detected by CCK-8 assay, colony formation assay and Western blot assay.Results: After 24 h and 48 h administration, α-Hed at 10, 15 and 20 μmol/L significantly inhibited the proliferation viability of NSCLC cells (all P<0.01). Compared with the control group, the apoptosis rate significantly increased after 20 μmol/L α-Hed treatment (P<0.01).C-caspase-3 expression in NSCLC cells was upregulated (P<0.05) and Bcl-2 expression was downregulated after α-Hed administration. The targets of AKT1, STAT3, EGFR and JAK2 with the binding affinity less than -5 kcal/mol were screened out via network pharmacology and molecular docking. Western blot showed that the expressions of EGFR, p-AKT/AKT, p-STAT3/STAT3 and JAK2 proteins in A549 and H1299 cells were significantly downregulated after α-Hed treatment (all P<0.05). Furthermore, α-Hed in combination with DDP more significantly inhibited the proliferation of NSCLC cells (P<0.01) and downregulated the expression of EGFR, p-AKT/AKT, p-STAT3/STAT3 and JAK2 proteins (P<0.05 or P<0.01). Conclusion: α-Hed induces the apoptosis of NSCLC by down-regulating EGFR and JAK2 expressions, and inhibiting the phosphorylation of STAT3 and AKT. Especially, the inhibitory effect is enhanced when α-Hed is used in combination with DDP, and the EGFR/AKT and JAK2/STAT3 pathways are further inhibited.
Keywords:
Project Supported:
Clc Number:
