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.