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College of Medicine/School of Medicine (의과대학/대학원)
Internal Medicine (내과학전공)
Journal Papers (저널논문_내과학전공)
Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis
- Authors
- Kim, Seongyeong ; Min, Ahrum ; Lee, Kyung-Hun ; Yang, Yaewon ; Kim, Tae-Yong ; Lim, Jee Min ; Park, So Jung ; Nam, Hyun-Jin ; Kim, Jung Eun ; Song, Sang-Hyun ; Han, Sae-Won ; Oh, Do-Youn ; Kim, Jee Hyun ; Kim, Tae-You ; Hangauer, David ; Lau, Johnson Yiu-Nam ; Im, Kyongok ; Lee, Dong Soon ; Bang, Yung-Jue ; Im, Seock-Ah
- Issue Date
- 2017-07
- Citation
- Cancer Research and Treatment, Vol.49 No.3, pp.643-655
- Keywords
- Src kinase inhibitor ; Mitotic catastrophe ; Microtubules ; KX-01 ; Triple negative breast neoplasms
- 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 MU 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 phos-pho-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.
- ISSN
- 1598-2998
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