Experimental study on the effect and mechanism of action of active immunization with elemene combo-tumor cell vaccine / 中国病理生理杂志

ABSTRACT

Elemene is a new anticancer drug isolated from a Chinese traditional medicine Curcuma aromatica. In previous work, we discovered that tumor cell vaccine (TCV) treated with oleum Curcuma aromatica or elemene could induce significant immunoprophylactic effect against a variety of aminal tumor strains and the method of preparation of elemene combo-TCV(EC-TCV) already got China's inventive patent. In this paper we further studied the active immunotherapeutic effect and the possible cellular/molecular mechanisms of EC-TCV immunization. The results were as follows:(1) EC-TCV immunization showed significant therapeutic effects (P＜0.05) against murine Ca761 syngeneic mammary carcinoma (H-2k) and HCa-F allogeneic hepatic carcinoma (H-2-) models; (2) The spleen cells of Hca-F EC-TCV immunized mice displayed higher cytotoxicity and IL-12 level while the secretion of IL-10 was decreased (P＜0.05); (3) Similar to heat shock, elemene(E), mitomycin C(MMC) and glutaraldehyde (G) could act alone as stressor, and induce significant changes of the expression of membrane heat shock proteins(HSP70 or/and HSP90) on L615 leukemia and HCa-F hepatoma cells and the EC-TCVs (E+MMC+G treated in combination) showed the highest level of membrane HSPs expression (P＜0.05 or P＜0.01 );(4) The HSP70-peptide complex isolated from HCa-F EC-TCV through ADP-agarose affinity chromatographic system could induce active immunoprotection against lethal dose challenge of HCa-F hepatic cancer cell but could not protect against the cross challenge of lethal dose of L615 leukemia. The results indicated that the immunoprotective effect of EC-TCV was in some extent tumor-specific, MHC-nonrestricted, and HSPs might play an important role in its molecular mechanisms.