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Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment ; : 643-655, 2017.
Article Dans Anglais | WPRIM | ID: wpr-167303
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.
Sujets)

Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Tubuline / Cicatrisation de plaie / Techniques in vitro / Tumeurs du sein / Cycle cellulaire / Lignée cellulaire / Technique d'immunofluorescence / Src-Family kinases / Points de contrôle du cycle cellulaire / Hétérogreffes Limites du sujet: Animaux langue: Anglais Texte intégral: Cancer Research and Treatment Année: 2017 Type: Article

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Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Tubuline / Cicatrisation de plaie / Techniques in vitro / Tumeurs du sein / Cycle cellulaire / Lignée cellulaire / Technique d'immunofluorescence / Src-Family kinases / Points de contrôle du cycle cellulaire / Hétérogreffes Limites du sujet: Animaux langue: Anglais Texte intégral: Cancer Research and Treatment Année: 2017 Type: Article