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Cancer Chemother Pharmacol. 2018 Jan;81(1):207-216. doi: 10.1007/s00280-017-3493-4. Epub 2017 Dec 1.

The earlier, the better: the effects of different administration timepoints of sorafenib in suppressing the carcinogenesis of VEGF in rats.

Author information

1
Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, 58th Zhongshan Road II, Guangzhou, 510080, People's Republic of China.
2
The Central Hospital of Wuhan, Wuhan, People's Republic of China.
3
Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, 58th Zhongshan Road II, Guangzhou, 510080, People's Republic of China. cir.huangyonghui@vip.163.com.

Abstract

PURPOSE:

To investigate the optimal starting time point of sorafenib therapy in suppressing the tumor-promoting effects of VEGF up-regulation, which is frequently found after local therapy in clinical practice.

METHODS:

VEGF was intravenously injected to imitate the evaluated expression after local tumor therapy, such as TACE. A total of 40 SD rats bearing hepatic tumors were randomly divided into four groups and sorafenib was administered at different timepoints: (A) control group: VEGF injection only; (B) initiating sorafenib 72 h prior to VEGF injection; (C) initiating sorafenib simultaneously with VEGF injection; (D) initiating sorafenib 72 h post-VEGF injection. The rate of tumor growth, median survival time, expression of VEGF, and microvessel density (MVD), as determined by immunohistochemical (IHC) examination, were compared.

RESULTS:

The results revealed that the tumor size and median survival time were significantly different between the three sorafenib groups compared to the control group (p < 0.05). Median survival times were 19.6 ± 1.78, 31.2 ± 6.99, 27.4 ± 4.9, and 26.5 ± 4.6 days in group A, B, C, and D, respectively. Furthermore, there was a difference in statistical significance between the two sorafenib groups B and D (p = 0.04). Tumors were collected for HE staining and IHC examination. The expression levels of VEGF in B, C, and D were 42.8 ± 7.96, 71.9 ± 15.73, and 73.6 ± 13.73, and all of them were significantly lower than that in the control group (88.3 ± 13.61). Furthermore, the level of MVD was 109.2 ± 8.98 in the control group, which was significantly higher than in the three sorafenib groups (45.7 ± 16.92, 77.1 ± 16.29, and 93.6 ± 12.87, all p < 0.05).

CONCLUSIONS:

According to our results, the most suitable regimen for the administration of sorafenib is before the increased expression of VEGF, which showed a potential advantage for controlling the tumor growth and prolonging the survival time of test animal via inhibiting VEGF-receptor expression through the bifunction of VEGF, and the reduction of tumor angiogenesis.

KEYWORDS:

Liver tumor; Microvessel density; Overall survival time; Sorafenib; Vascular endothelial growth factor

PMID:
29196964
PMCID:
PMC5754402
DOI:
10.1007/s00280-017-3493-4
[Indexed for MEDLINE]
Free PMC Article

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