Enrichment of Isaria felina Culture with Selenium Enhances its in vivo Antitumor Effects on H22 Hepatoma via Decreasing the Expression of VEGF

Abstract

Background: The polysaccharide extract of C. sinensis, Isaria felina (IF), has antitumor effects. Selenium (Se) can improve disease prevention and reduce the toxicity of toxic elements, but the effect of Se-enriched IF on hepatoma remains unknown.

Objective: To determine the organic transformation of Se and compare the antitumor effects between Se-enriched IF (IF-Se) and IF on xenograft H22 hepatoma-bearing mice.

Methods: Se was added to the solid-state culture medium, and the organic Se content was detected by HPLC-ICP-MS. Forty-two Kunming mice were randomly divided into seven groups to test the antitumor effects of low- (300 mg/kg) and high- (600 mg/kg) doses of IF-Se and IF through xenograft. Huai'er granules were administered as the positive control. In addition, interleukin (IL)-2 and vascular endothelial growth factor (VEGF) expressions were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry method.

Results: The conversion rate in the IF-Se70, IF-Se140, and IF-Se280 groups were 91.5%, 93.4%, and 89.3%, respectively. Therefore, IF-Se140 was used to carry out the subsequent experiments. The tumor inhibition rates of IF-Se were significantly higher compared with IF (P < 0.05). Moreover, the spleen coefficient, IL-2, and VEGF expression levels significantly decreased (all Ps < 0.05), and the thymus coefficient significantly increased (P < 0.05) in the high-dose IF-Se group compared with the model control group.

Conclusion: The inhibitory effects of IF on H22 hepatoma-bearing mice were enhanced after Se enrichment. Therefore, Se-enriched IF might be a new strategy for treating hepatoma.

Keywords: Anti-tumor effects; Isaria felina; hepatoma cells; interleukin 2; selenium-enriched culture; vascular endothelial growth factor.