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The therapeutic effect of ultrasound targeted destruction of schisandrin A contrast microbubbles on liver cancer and its mechanism

Xiaohui Wang
Xiaohui Wang
, 
Feng Wang
Feng Wang
, 
Pengfei Dong
Pengfei Dong
 und 
Lin Zhou
Lin Zhou
   | 07. März 2024
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Article Category: Research Article
Online veröffentlicht: 07. März 2024
Seitenbereich: 221 - 233
Eingereicht: 20. Sept. 2023
Akzeptiert: 26. Dez. 2023
DOI: https://doi.org/10.2478/raon-2024-0019
Schlüsselwörter
© 2024 Xiaohui Wang et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

FIGURE 1.

Analytical characterization of Span and polyethylene glycol (Span-PEG) microbubbles loaded with schisandrin A (A) The structure SEM of schisandrin A microbubbles; (B) The particle size distribution; (C) Zeta potential of schisandrin A microbubbles, (n = 6).
Analytical characterization of Span and polyethylene glycol (Span-PEG) microbubbles loaded with schisandrin A (A) The structure SEM of schisandrin A microbubbles; (B) The particle size distribution; (C) Zeta potential of schisandrin A microbubbles, (n = 6).

FIGURE 2.

The Walker-256 cell survival rate of schisandrin A (n = 6; compared with control group [0 μg/mL], **P < 0.01).
The Walker-256 cell survival rate of schisandrin A (n = 6; compared with control group [0 μg/mL], **P < 0.01).

FIGURE 3.

Anti-tumor cell experiment assessment in different groups (n = 6; *Compared with C group, P < 0.01; &Compared with D group, P < 0.01; #Compared with U+D group, P < 0.01)
Anti-tumor cell experiment assessment in different groups (n = 6; *Compared with C group, P < 0.01; &Compared with D group, P < 0.01; #Compared with U+D group, P < 0.01)

FIGURE 4.

The content of schisandrin A in the cells of each group (A. Chromatogram of standard schisandrin A; B. Chromatogram of blank intracellular fluid; C. Chromatogram of blank intracellular solution + standard schisandrin A; D. Chromatogram of the tested intracellular liquid; E. Comparison of drug concentrations between different groups, n = 6; **Compared with C group P < 0.001; ##Compared with D group P < 0.001)
The content of schisandrin A in the cells of each group (A. Chromatogram of standard schisandrin A; B. Chromatogram of blank intracellular fluid; C. Chromatogram of blank intracellular solution + standard schisandrin A; D. Chromatogram of the tested intracellular liquid; E. Comparison of drug concentrations between different groups, n = 6; **Compared with C group P < 0.001; ##Compared with D group P < 0.001)

FIGURE 5.

The changes in tumor size before and after drug treatment detected by Ultrasound images (n = 6; *Compared with Pre-treatment group, P < 0.05; **Compared with Pre-treatment group, P < 0.01).
The changes in tumor size before and after drug treatment detected by Ultrasound images (n = 6; *Compared with Pre-treatment group, P < 0.05; **Compared with Pre-treatment group, P < 0.01).

FIGURE 6.

Detection of serum inflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], interleukin-1β [IL-1β]) in different group (n = 6, *Compared with C group, P < 0.01; #Compared with D+U group, P < 0.01; &Compared with M+U group, P < 0.01).
Detection of serum inflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], interleukin-1β [IL-1β]) in different group (n = 6, *Compared with C group, P < 0.01; #Compared with D+U group, P < 0.01; &Compared with M+U group, P < 0.01).

FIGURE 7.

Histopathological changes in different groups (division of the tumor cell nucleus [red arrows], hyperplasia of collagen fibers [green arrows], necrosis of tumor cells [yellow arrows], and balloon-like swelling of tumor cells [blue arrows]).
Histopathological changes in different groups (division of the tumor cell nucleus [red arrows], hyperplasia of collagen fibers [green arrows], necrosis of tumor cells [yellow arrows], and balloon-like swelling of tumor cells [blue arrows]).

FIGURE 8.

Immunohistochemical changes in different groups.
Immunohistochemical changes in different groups.

FIGURE 9.

The expression of hypoxia inducible factor-1α (HIF-1α), vascular endothlial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2) proteins in the tumor tissues (n = 6, *Compared with C group, P < 0.01; #Compared with D+U group, P < 0.01; &Compared with M+U group, P < 0.01)
The expression of hypoxia inducible factor-1α (HIF-1α), vascular endothlial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2) proteins in the tumor tissues (n = 6, *Compared with C group, P < 0.01; #Compared with D+U group, P < 0.01; &Compared with M+U group, P < 0.01)

FIGURE 10.

Protein expression results of phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway in tumor tissues (n = 6, *Compared with Control, P < 0.05; **Compared with Control, P < 0.01).
Protein expression results of phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway in tumor tissues (n = 6, *Compared with Control, P < 0.05; **Compared with Control, P < 0.01).

Loading rate of schisandrin A in Span and polyethylene glycol (Span-PEG) composite microbubbles

Number of experiments Absorbance value Rate of load/%
1 0.524 8.68
2 0.536 8.88
3 0.541 8.96
Mean 0.534 8.84
SD 0.009 0.14
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