Replies

Via patriots.win (long):

novel MDR reversal agents that could be further used clinically for the treatment of the resistant cancers.

Avermectins, a class of 16-membered macrolide compounds, are widely used to treat parasites and pest insects [15]. Ivermectin (IVM), an avermectin derivative, was found to be especially effective against a variety of parasites and disease vectors that could be used in humans [16,17,18]. Recently, IVM has been found to inhibit the growth of some human cancer cells [19, 20]. In addition, IVM was also found to inhibit the ATPase activity of P-gp [21, 22] and reverse the P-gp-related multidrug resistance in vitro [21, 23, 24]. However, the detailed underlying mechanisms of how IVM enhances the sensitivity of the cells to the chemotherapeutic agents and reverses the resistance of the tumor cells remain largely unknown. And whether IVM could reverse the multidrug resistance in vivo has not been elucidated.

In this study, we used multiple tumor cell lines, including vincristine (VCR)-sensitive/resistant HCT-8 colorectal cancer cells, adriamycin (ADR)-sensitive/resistant MCF-7 breast adenocarcinoma cells and ADR-sensitive/resistant K562 chronic myeloid leukemia cells, as well as two xenograft tumor models, to investigate whether IVM could reverse the drug resistance of cancer cells. These cancer cell lines were used because both colorectal cancer and breast adenocarcinoma are among the most common malignant solid tumors [25, 26], and chronic myeloid leukemia (CML) is one of the most common malignant hematological neoplasms [27]. In this study, we found that IVM could increase the sensitivity of the cancer cells and, in particular, the resistant cancer cells to the chemotherapeutic drugs and even reverse the resistance of the cancer cells to the drugs both in vitro and in vivo, and we identified a novel molecular mechanism underlying the reversal of the chemotherapeutic drug-resistance by IVM in cancer cells.

https://jeccr.biomedcentral.com/articles/10.1186/s13046-019-1251-7