Immuno-modulatory and cellular antioxidant activities of κ-selenocarrageenan in combination with Epirubicin in H22 hepatoma-bearing mice.

Abstract

Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The aim of this study is to evaluate the synergistic anti-tumor effects and underlying mechanism of κ-selenocarrageenan (KSC) in combination with the chemotherapy drug epirubicin (EPI) in H22 tumor-bearing mice. Hepatocellular carcinoma H22 cells were implanted into mice. After the transplants were successfully established, the animals were divided into four groups: namely the control group, the KSC group, the EPI group and the KSC+EPI group. The effects of KSC and EPI on tumor growth, survival time, thymus index, spleen index, white blood cells (WBC), splenocyte proliferation, natural killer (NK) cell activity, serum TNF-α and IL-2 levels, and antioxidant enzymes in the liver cells were determined. KSC and/or EPI significantly reduced tumor weight and prolonged the survival time. Furthermore, KSC could attenuate EPI-induced atrophy in the thymus and spleen, as well as other toxicities, which may indicate an additive effect of this combination against organ dysfunction and cellular injury. KSC significantly promoted Con A- and LPS-stimulated splenocyte proliferation, enhanced NK cell activity, and reversed the inhibition of NK activity induced by EPI (P<0.01). In addition, KSC could elevate serum TNF-α and IL-2 levels, increase the GSH-Px, SOD, CAT and GSH activity levels in liver tissue, and reduce MDA content. These results suggest that KSC can regulate immune function in mice and suppress the growth of tumor in H22 tumor-bearing mice, and its synergistic antitumor activity with epirubicin may be related to its antioxidant and immuno-modulatory effects.