Ontology highlight
ABSTRACT: Purpose
KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo.Materials and methods
The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects.Results
KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho-Src and proliferative-signaling molecules were down-regulated in KX-01-sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01-induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01-sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model.Conclusion
KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.
SUBMITTER: Kim S
PROVIDER: S-EPMC5512373 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
Kim Seongyeong S Min Ahrum A Lee Kyung-Hun KH Yang Yaewon Y Kim Tae-Yong TY Lim Jee Min JM Park So Jung SJ Nam Hyun-Jin HJ Kim Jung Eun JE Song Sang-Hyun SH Han Sae-Won SW Oh Do-Youn DY Kim Jee Hyun JH Kim Tae-You TY Hangauer David D Lau Johnson Yiu-Nam JY Im Kyongok K Lee Dong Soon DS Bang Yung-Jue YJ Im Seock-Ah SA
Cancer research and treatment 20161006 3
<h4>Purpose</h4>KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 <i>in vitro</i> and <i>in vivo</i>.<h4>Materials and methods</h4>The antitumor effect of KX-01 in triple negative breast cancer ...[more]