Antitumor and antimetastatic activities of vaccine prepared from cisplatin-resistant lewis lung carcinoma.

AIM: To study antitumor and antimetastatic activities of antitumor vaccine (ATV) prepared from cisplatin (CP) sensitive and resistant strains of Lewis lung carcinoma (LLC). METHODS: The inhibition of tumor growth, and the mean survival time of the tumor-bearing animals, the number and the volume of metastases were measured as the indices of ATV efficacy. The activity of cytotoxic T-lymphocytes and natural killer cells, peritoneal macrophages (Mph), the level of tumor necrosis factor and the total proteolytic activity of blood plasma (PA) were assessed. RESULTS: ATV from CP resistant LLC prepared using cytolectin (CL) of capital VE, Cyrillic. subtilis capital VE, Cyrillic-7025 significantly inhibited growth of CP resistant tumors (by 52%) and increased mean survival time (MST) of animals (by 44.6%). The index of metastasis inhibition for ATV prepared from CP sensitive or resistant LLC was 154.5% and 227.0%, respectively. In all vaccine-treated animals, Mph activity was shown to be significantly increased. In spite of high antitumor and antimetastatic effects of ATV prepared from CP resistant LLC, PA in plasma of animals inoculated with CP resistant LLC was increased significantly upon vaccine administration.

Total proteolytic activity and levels of the main proteinase inhibitors in blood plasma of mice bearing Lewis lung carcinoma upon development of resistance to cisplatin.

UNLABELLED: The aim of the study was to evaluate the total proteolytic activity (TPA) and the content of alpha-1-proteinase inhibitor (alpha1PI) and alpha-2-macroblobulin (alpha2M) in the blood plasma of mice with Lewis lung carcinoma (LLC) upon the development of resistance to cisplatin. METHODS: Experimental LLC model with different sensitivity to cisplatin was obtained by sequential subcutaneous transplantation of LLC cells from cisplatin-treated animals. TPA, alpha1PI and alpha2M levels were evaluated by standard biochemical methods. RESULTS: It has been shown that the development of LLC resistance to cisplatin is accompanied by the increase of TPA activity and the level of the main proteinase inhibitor - alpha1PI. Despite the high level of alpha1PI in the resistant variant of LLC compared to parental tumor, the increase of TPA/alpha1PI ratio indicated the deficiency of that inhibitor in the blood of mice bearing cisplatin-resistant tumors, that promotes metastasis. The growth of both resistant to cisplatin LLC and sensitive variant was accompanied with the reduction of the alpha2M concentration. CONCLUSIONS: Upon the development of resistance to cisplatin in vivo the shift in the balance between proteinases and their inhibitors toward activation of TPA simultaneously with the increased metastasis is taking place.