Lijuan Lu

Loureirin B inhibits Cervical Cancer Development by Blocking PI3K/AKT Signaling Pathway: Network Pharmacology Analysis and Experimental Validation

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.

PLGA‐PEG‐c(RGDfK)‐ Kushenol E Micelles With a Therapeutic Potential for Targeting Ovarian Cancer

Background: As a naturally derived inhibitor of autophagy, Kushenol E (KE) is a biprenylated flavonoid and is isolated from Sophora flavescens , which has been used for the treatment of cancer, hepatitis, and skin diseases. However, KE, as a poorly soluble drug, exhibited strong autophagy regulating activity in in vitro cancer cell lines, but no related studies have reported its antiovarian cancer property. Therefore, it is very beneficial to enhance the antineoplastic properties of KE by establishing an ovarian tumor‐targeting nanoparticle system modified with tumor‐homing c(RGDfK) peptides. Materials and Methods: In the current study, poly(lactic‐co‐glycolic acid)‐poly(ethylene glycol)‐modified with cyclic RGDfK peptide (PLGA‐PEG‐c(RGDfK))‐KE micelles (PPCKM) were prepared to overcome the poor water solubility of KE to meet the requirement of tumor‐active targeting. The effect of PPCKM on ovarian cancer was evaluated on SKOV‐3 cells and xenograft models in BALB/c nude mice. Results: The PPCKM showed a higher drug cumulative release ratio (82.16 ± 7.69% vs. 34.96 ± 3.05%, at 1.5 h) with good morphology, particle size (93.41 ± 2.84 nm), and entrapment efficiency (89.7% ± 1.3%). The cell viability, migration, and apoptosis analysis of SKOV‐3 cells demonstrated that PPCKM retained potent antitumor effects and promoted apoptosis at early and advanced stages with concentration‐dependent. Based on the establishment of xenograft models in BALB/c nude mice, we discovered that PPCKM reduced tumor volume and weight, inhibited proliferating cell nuclear antigen (PCNA) and Ki67 expression, as well as promoted apoptosis by targeting the tumor site. Conclusion: The findings in this study suggest that PPCKM may serve as an effective therapeutic option for ovarian cancer.