[Modification of antitumor effect of vincristine by natural avermectins].

The effect of avermectins (aversectin C, aversectin C1 and avermectin B1) on the vincristine antitumor action with respect to murine transplantable tumors was studied. It was shown that both the natural avermectins mixtures and the individual avermectin B1 potentiated the antitumor action of vincristine on Ehrlich carcinoma, melanoma B16 and P388 lymphoid leukemia, including the vincristine resistant strain P388. Such an effect of the avermectins was observed only when they were administered after vincristine.

[Antitumor effect of natural avermectins].

The effects of the natural avermectin complex, aversectin C and individual avermectin B1 on the growth of ascitic and solid transplantable tumors in animals were studied. The results showed for the first time that both aversectin C and avermectin B1 possessed marked antitumor activity. In subtoxic doses aversectin C significantly inhibited the growth of P388 lymphoid leukemia and Ehrlich carcinoma, both ascitic and solid ones.

Antitumor effect of avermectins.

The effect of a mixture of naturally occurring aversectin C and avermectin B(1) on the growth of ascites and solid experimental tumors of mice was studied. It was shown for the first time that avermectins possess a pronounced antitumor action. When added at nontoxic doses, they significantly suppressed the growth of ascites Ehrlich carcinoma and P388 lympholeukemia and solid Ehrlich and 755 carcinomata.

Avermectins inhibit multidrug resistance of tumor cells.

The modification of the sensitivity of Hep-2 and P388 tumor cells to taxol and vincristine, substrates of multidrug resistance proteins, by naturally occurring avermectins and the effect of avermectins on the accumulation of calcein in cells and the efflux of rhodamine 123 were studied. While avermectins did not affect the sensitivity of tumor cells to hydrogen peroxide and cisplatin, they significantly enhanced the sensitivity of cells of both wild-type and resistant strains to taxol and vincristine. The coefficients of modification for resistant strains were substantially higher.