Conjugates of carminomycin (Cm) with α-fetoprotein (AFP) and epidermal growth factor (EGF) were prepared and their cytotoxic activities were studied in vitro. Both conjugates showed cytotoxic activity which exceeded that of free Cm in tumor cell cultures of MCF-7, SKOV3, QOS, P388 and B16 cells. The antitumor effects of the conjugates were studied in vivo in mice with subcutaneous tumors of B16 and P388 cells. The Cm-AFP and Cm-EGF conjugates inhibited tumor growth and noticeably increased the mean life span in experimental animals. Our results suggest that the therapeutic activity of Cm can be significantly enhanced by conjugation to AFP or EGF.
Recombinant human MIS (rhMIS) produced in transfected Chinese hamster ovary cells has been purified by immunoaffinity chromatography. In the absence of reducing agents, 140 kD homodimer and several oligomers with molecular masses from 280 to 1000 kD are present. Homodimer, tetramer, and higher-molecular-weight rhMIS fractions reduced survival of tumor cells. For these experiments, FITC-labeled rhMIS was used for binding and endocytosis studies by flow cytometry. Flow cytometry performed on MIS-sensitive cancer cell lines demonstrated specific binding of rhMIS. The majority of rhMIS receptors have cytosolic localization. Thus, the level of MIS receptors on the cell membrane was proportional to the content of MIS-binding proteins in the whole cell and defines a level of receptor-mediated endocytosis. The immunopurified rhMIS caused significant growth inhibition of ovarian and prostate adenocarcinoma and melanoma human cell lines in inhibition assays.
Biodegradable polymeric nanoparticles conjugated with targeting vector molecules have become prospective agents to improve the effectiveness of chemotherapeutic cancer treatment. This approach reduces the systemic toxicity of the drugs and increases the specificity of their uptake by cancer cells. A method has been developed to obtain complex nanoparticles loaded with the antitumor drug paclitaxel and a C terminal fragment of recombinant oncofetal alpha fetoprotein serving as a vector molecule, the in vitro cytotoxic activity of complex nanoparticles for MCF 7 human breast adenocarcinoma cells and resistant MDR1 + cells of the MCF 7 Adr subline was shown to be higher than the cytotoxicity of the free drug and drug loaded nano particles without the vector molecule. Moreover, the toxicity of complex paclitaxel loaded nanoparticles against lymphocytes was low, which confirmed the selectivity of nanoparticle action. In summary, these results demonstrate that the strategy of active targeting of nanoparticles can efficiently enhance the antitumor activity of paclitaxel and it can solve the problem of reversing the multidrug resistance (MDR) of tumor cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.