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- Title
Loureirin B inhibits Cervical Cancer Development by Blocking PI3K/AKT Signaling Pathway: Network Pharmacology Analysis and Experimental Validation.
- Authors
Hong, Yinwen; Sun, Xueliang; Lu, Lijuan
- Abstract
Loureirin B (LB) is an iconic component of Chinese dragon's blood that presents anti-cancer effects in gastric cancer and liver cancer. Although LB has shown benefits in treating several disorders such as cardiac fibrosis, cerebral ischemia/reperfusion, and osteoporosis, its effect on cervical cancer remains unknown. This study aimed to investigate the effects and mechanisms of LB on treating cervical cancer. A CCK-8 assay was conducted to determine the influence of LB on the viability of HeLa cells. Colony formation assay was performed to verify the impact of LB on HeLa cell proliferation. Cell cycle and apoptosis were detected by flow cytometry and western blot. The scratch assay, Transwell assay and western blot were used to examine the migration and invasion capacity of HeLa cells. The potential targets and signaling pathways of LB treating cervical cancer were predicted by network pharmacology analysis and subsequently validated in vitro. The results showed that the HeLa cell viability gradually declined to 64.83% for 12 h, 53.17% for 24 h, and 42.38% for 48 h after treatment with 5–80 μg/mL LB. Treatment with 20 μg/mL LB decreased cell colonies from 156.7 ± 11.7 to 102.7 ± 5.7. LB arrested cell cycle by reducing the expressions of Ki-67 and PCNA. Compared to the cell apoptosis rate of 2.63% in control group, LB increased it to 6.59% via upregulating Bax and suppressing Bcl-2 expressions. Additionally, LB reduced the invasion and migration capacity of HeLa cells by decreasing MMP-2 and MMP-9 levels. Network pharmacology analysis revealed that LB might suppress the PI3K/AKT signaling pathway to exert the aforementioned effects, as evidenced by a PI3K agonist attenuating the effects of LB on HeLa cells. In conclusion, this study demonstrated that LB inhibited the proliferation of cervical cancer cells, induced its apoptosis, and reduced its invasion and migration via targeting the PI3K/AKT signaling pathway.
- Subjects
MEDICAL sciences; CELL cycle; CANCER cell proliferation; CERVICAL cancer; LIVER cancer; CELL migration; HELA cells
- Publication
Applied Biochemistry & Biotechnology, 2024, Vol 196, Issue 12, p8587
- ISSN
0273-2289
- Publication type
Academic Journal
- DOI
10.1007/s12010-024-04975-7