WX-132-18B, a novel microtubule inhibitor, exhibits promising anti-tumor effects

Abstract

Cancer drug researchers have been seeking microtubule-inhibiting agents (MIAs) with higher bioactivity and lower toxicity than currently marketed drugs. WX-132-18B, a novel structural compound synthesized at our institute, specifically bound to the colchicine-binding site on tubulin rather than the vinblastine site, and concentration-dependently reduced microtubule content via depolymerization. It exhibited the same cellular phenotypic profiles as the classic MIAs (colchicine, vincristine, and taxol), including inducing cell cycle arrest at the G2/M phase, triggering tumor cell apoptosis, promoting nuclear membrane permeability, reducing mitochondrial membrane potential, and disrupting the redox system balance. Importantly, WX-132-18B displayed more potent in vitro bioactivity (IC50 0.45–0.99 nM) than did the classic MIAs; it inhibited the proliferation of human umbilical vein endothelial cells and seven types of human tumor cells, especially the taxol-resistant breast cancer cells MX-1/T. WX-132-18B also dose-dependently inhibited mice sarcoma, human lung, and gastric cancer xenograft tumors and the formation of tumor blood vessels in mice. In conclusion, WX-132-18B is a novel microtubule-depolymerizing agent that selectively acts on the colchicine-binding site of tubulin and exerts potent in vitro and in vivo anti-tumor effects. These characteristics, along with its anti-angiogenesis and anti-drug resistance properties, make WX-132-18B a promising anti-tumor drug candidate.

MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

“…Following the full attachment of cells to the bottom of the plates, the cells were treated with the indicated concentrations of molecular targeted agents (i.e., 10, 3, 1, 0.3, 0.1, 0.03, and 0.01 μmol/l) for 48 h. Subsequently, the cells were analyzed through Thiazolyl Blue Tetrazolium Bromide [3-(4,5-dimethyl-2thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] (MTT) analysis following previously described methods 42 . The inhibition rate was calculated as follows: (optical density [OD] 490 nm control group − OD 490 nm administration group)/(OD 490 nm control group) 43,44 .…”

FBI-1 enhanced the resistance of triple-negative breast cancer cells to chemotherapeutic agents via the miR-30c/PXR axis

“…The TNBC cells were treated with the indicated concentration of agents (10, 3, 1, 0.3, 0.1, 0.03, or 0.01 μmol/L for olaparib) for 48 h. Then, cells were analyzed by the Sulforhodamine B (SRB) assay, following the methods provided by and Li et al 23 and Guan et al 24 . The relative survival cells were determined by the O.D.…”

“…The inhibition rates were calculated as (A 510nm-control of 48 h − A 510nm-compound of 48 h)/(A 510nm-control of 48 h − A 510nm-control of 0 h) * 100 23,24 . The IC 50 values of agents were calculated from the inhibition rates 23,24 . The colony formation experiments were performed following the method desicripted by Fang et al 5 .…”

<p>miR-596 suppresses the expression of Survivin and enhances the sensitivity of osteosarcoma cells to the molecular targeting agent anlotinib</p>

“…23 The inhibition rates of antitumor agents on cells were calculated, following the methods provided by Feng et al (2018). 19 The half-maximal inhibitory concentration values (IC 50 values) were calculated based on inhibition rates, following the methods described by Guan et al (2017) and Li et al (2018). 24,25 Antibodies and Western blot Antibodies to Survivin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were obtained from Abcam (Cambridge, UK).…”

“…19 The half-maximal inhibitory concentration values (IC 50 values) were calculated based on inhibition rates, following the methods described by Guan et al (2017) and Li et al (2018). 24,25 Antibodies and Western blot Antibodies to Survivin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were obtained from Abcam (Cambridge, UK). OSA cells transfected with control, miR-596, miR-596 + Survivin Mut , or miR-596 + inhibitor were harvested 48 hrs following transfection, and total protein samples were extracted for Western blot experiments.…”