[Explore the mechanism of astragaloside IV-PESV on proliferation, migration, and autophagy of prostate cancer cells based on the PI3K/AKT signaling pathway].

ABSTRACT

OBJECTIVE: Explore the effects of Astragaloside IV and Scorpion Venom Peptide on the activity, migration, apoptosis, cell cycle, autophagy, and the expression of proteins related to the PI3K/AKT signaling pathway in prostate cancer cells. METHODS: The human prostate cancer cell lines LNCaP and PC-3 were randomly divided into blank control group, Astragaloside IV group, Scorpion Venom Peptide group, Astragaloside IV-Scorpion Venom Peptide group, and rapamycin (positive drug group). After corresponding drug treatments for 24 hours, logarithmic growth phase tumor cells were collected for testing. Cell proliferation was assessed using a Cell Counting Kit-8 (CCK-8) assay, Transwell assay, apoptosis assay, cell cycle assay, and immunofluorescence analysis were performed to detect the activity and migration capacity of prostate cancer cells in each group, as well as their effects on apoptosis, cell cycle, and the autophagy target LC3. Western blot analysis was employed to measure the protein expression levels of p-PI3K, p-Akt, p-mTOR, Beclin1, LC3, and P62. RESULTS: Compared to the blank control group, the Astragaloside IV-Scorpion Venom Peptide group exhibited a significant decrease in the activity of prostate cancer cells (P<0.05) and a reduction in the cell invasion ability (migration capacity) (P<0.05). The early apoptosis rate (LR), late apoptosis rate (UR), and total apoptosis rate all increased (P<0.05). The proportion of cells in the G1 phase increased (P<0.05), while the proportion in the G2+S phase decreased (P<0.05). The immunofluorescence expression of LC3 significantly increased (P<0.05). The expression of LC3Ⅱ and Beclin1 proteins in prostate cancer cells LNCaP and PC-3 was upregulated (P<0.05), while the expression of P62, p-PI3K, p-AKT, and p-mTOR proteins was downregulated (P<0.05).Astragaloside IV-Scorpion Venom Peptide is superior to the Astragaloside IV group or Scorpion Venom Peptide group alone in inhibiting the activity and migration capacity of prostate cancer cells, suppressing cell mitosis, promoting early apoptosis, upregulating the expression level of LC3, and inhibiting the PI3K/AKT pathway while promoting autophagy (P<0.05). CONCLUSION: The mechanism by which Astragaloside IV-Scorpion Venom Peptide inhibits the proliferation and migration of prostate cancer cells, suppresses cell mitosis, promotes early apoptosis, and enhances autophagy may be related to the inhibition of the PI3K/AKT pathway.