Antitumor effects and the mechanisms of dual-targeting drug NL-101 on human multiple myeloma
10.11665/j.issn.1000-5048.20170412
- VernacularTitle:双靶点药物NL-101的抗多发性骨髓瘤活性及其机制研究
- Author:
Lan YANG
;
Qiufu GE
;
Dianwu GUO
;
Weiliang XU
;
Li ZHAO
- Keywords:
NL-101;
DNA damage;
HDAC inhibitor (HDACi);
dual-targeting;
antitumor activity
- From:
Journal of China Pharmaceutical University
2017;48(4):469-475
- CountryChina
- Language:Chinese
-
Abstract:
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.
