Antitumor effects and the mechanisms of dual-targeting drug NL-101 on human multiple myeloma / 中国药科大学学报

The antitumor activities of NL-101,aHDACi/DNA damage dual-targeting drug,on human multiple myeloma in vitro and in vivo were studied.Furthermore,the primary mechanisms were revealed.We detected the anti-proliferative activity of NL-101 on 10 human multiple myeloma cell lines,and the combinational effect of NL-101 and bortezomib on RPMI 8226 cell line.The inducing effects of NL-101 on cell cycle arrest and apoptosis were detected by FACS.The effects of NL-101 on acetyled-Histone H3,total Histone H3,acetyled α-Tubulin,total α-Tubulin,phospho-Histone H2A.X and total Histone H2A.X were evaluated by Western blott.We also demonstrated the antitumor activity of NL-101 and the combinational effect of NL-101 and bortezomib on RPMI 8226 xenograft tumor model in vivo.Results showed that NL-101 possessed strong antitumor activities on human multiple myeloma cells in vitro and in vivo.NL-101exhibited significant HDAC inhibitory activity and DNA alkylating activity.NL-101not only inhibited histone deacetylation level,but also increased the DNA damage in multiple myeloma cells.Meanwhile,NL-101 induced cell cycle arrest and apoptosis.Also,the synergistic effect of NL-101 was discovered when combined with bortezomib in vitro and in vivo.These data demonstrated that NL-101 may be a potent agent for the treatment of human multiple myeloma in future.

Extraction and purification of giant salamander skin mucous glycoprotein and study its anti-cancer activity of lung cancer / 中国生化药物杂志

Objective To study the appearance of skin mucous glycoprotein in vitro on the activity of human lung cancer cells A549. Methods Used alkali extraction and DEAE-52 ion exchange chromatography and Sephadex G-100 gel chromatography purification salamander mucous glycoprotein; Salamander mucous glycoprotein inhibition of human lung cancer cells A549 was detected by MTT colorimetric method in vitro.ResuIts It showed that the total sugar content in the appearance of mucus was 4.23%, the relatively pure glycoprotein component, by SDS protein electrophoresis tests, it contained a single glycoprotein component, its molecular weight was about 30 kDa.With glycoprotein pure concentration increased from 1,10, 20,40μg/mL, the glycoprotein inhibition rate of A549 cells increased; when the glycoprotein concentration was 40 μg/mL, for 24 h action, the inhibition rate of A549 cells was up to 85.66 %, while the role of 48 h, the inhibition rate of A549 cells was up to 92.32%.Inhibition effect of mucus glycoprotein on A549 cell compared with positive control drug, had significant difference.ConcIusion Salamander mucus glycoproteins of human lung cancer cells has obvious inhibitory effect, can provide theoretical basis for the development of lung cancer drug resistance.