Effect of Inhibiting Tumor Angiogenesis After Embolization in the Treatment of HCC with Apatinib-Loaded p(
HCC
PIB
apatinib
transcatheter arterial embolization
tumor angiogenesis
Journal
Journal of hepatocellular carcinoma
ISSN: 2253-5969
Titre abrégé: J Hepatocell Carcinoma
Pays: New Zealand
ID NLM: 101674775
Informations de publication
Date de publication:
2020
2020
Historique:
received:
15
09
2020
accepted:
11
12
2020
entrez:
7
1
2021
pubmed:
8
1
2021
medline:
8
1
2021
Statut:
epublish
Résumé
Transcatheter arterial embolization (TAE) is widely used in hepatocellular carcinoma (HCC) therapy. Tumor hypoxia often correlates with the recurrence and metastasis of the tumor and is the critical factor limiting the treatment effect of TAE. To investigate the underlying mechanism and therapeutic potential of TAE combined with apatinib-loaded p( Sixty-five VX2 tumor-burdened rabbits were randomly divided into five groups and treated transarterially with apatinib-loaded PIB (Group PA, 0.4 mL, n=13), PIB alone (Group P, 0.4 mL, n=13), iodized oil alone (Group I, 0.4 mL, n=13), apatinib solution (Group A, 0.4 mL, n=13) or saline (Group NS, 0.4 mL, n=13). The dose of apatinib was 2 mg/kg. Tumors were harvested, sectioned and immunohistochemically stained, and the tumor growth rates and survival times in each group were measured. Blood samples and liver tissues were collected for pharmacokinetic analysis. The tumor growth rate in Group PA was considerably lower than the other four groups (P=0.000<0.01), and the survival time was significantly prolonged (P=0.000<0.01). The immunohistochemistry results showed that CD31 expression was significantly lower in Group PA than that of the other four groups (P=0.000<0.01). The apatinib concentration in the blood fell below 10 ng/mL within 10 min after TAE and dropped below 1 ng/mL after 8 h. The drug was released continuously in the liver for 36 days, with the highest concentration at the tumor junction (P=0.045<0.05). PIB effectively targeted apatinib to HCC tissues, achieved a slow and sustained release of the drug in the tumor and considerably reduced the systemic drug concentration. Further experiments showed significantly prolonged survival times and an inhibitory effect on tumor growth.
Sections du résumé
BACKGROUND
BACKGROUND
Transcatheter arterial embolization (TAE) is widely used in hepatocellular carcinoma (HCC) therapy. Tumor hypoxia often correlates with the recurrence and metastasis of the tumor and is the critical factor limiting the treatment effect of TAE.
PURPOSE
OBJECTIVE
To investigate the underlying mechanism and therapeutic potential of TAE combined with apatinib-loaded p(
MATERIALS AND METHODS
METHODS
Sixty-five VX2 tumor-burdened rabbits were randomly divided into five groups and treated transarterially with apatinib-loaded PIB (Group PA, 0.4 mL, n=13), PIB alone (Group P, 0.4 mL, n=13), iodized oil alone (Group I, 0.4 mL, n=13), apatinib solution (Group A, 0.4 mL, n=13) or saline (Group NS, 0.4 mL, n=13). The dose of apatinib was 2 mg/kg. Tumors were harvested, sectioned and immunohistochemically stained, and the tumor growth rates and survival times in each group were measured. Blood samples and liver tissues were collected for pharmacokinetic analysis.
RESULTS
RESULTS
The tumor growth rate in Group PA was considerably lower than the other four groups (P=0.000<0.01), and the survival time was significantly prolonged (P=0.000<0.01). The immunohistochemistry results showed that CD31 expression was significantly lower in Group PA than that of the other four groups (P=0.000<0.01). The apatinib concentration in the blood fell below 10 ng/mL within 10 min after TAE and dropped below 1 ng/mL after 8 h. The drug was released continuously in the liver for 36 days, with the highest concentration at the tumor junction (P=0.045<0.05).
CONCLUSION
CONCLUSIONS
PIB effectively targeted apatinib to HCC tissues, achieved a slow and sustained release of the drug in the tumor and considerably reduced the systemic drug concentration. Further experiments showed significantly prolonged survival times and an inhibitory effect on tumor growth.
Identifiants
pubmed: 33409168
doi: 10.2147/JHC.S282209
pii: 282209
pmc: PMC7780989
doi:
Types de publication
Journal Article
Langues
eng
Pagination
447-456Informations de copyright
© 2020 Zhou et al.
Déclaration de conflit d'intérêts
The authors have declared that no competing interest exists.
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