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Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis. | LitMetric

AI Article Synopsis

  • KX-01 is a new cancer treatment that inhibits both Src and tubulin, showing potential advantages over previous Src inhibitors in treating triple negative breast cancer (TNBC).
  • The study assessed KX-01's effectiveness using various assays, revealing its ability to halt cell growth, reduce migration, and cause specific cell cycle changes in TNBC cell lines.
  • Results indicated that KX-01 not only suppressed tumor growth in cell cultures but also effectively delayed tumor progression in a mouse model, highlighting its promising antitumor properties.

Article 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 and .

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 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 using a mouse xenograft model.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512373PMC
http://dx.doi.org/10.4143/crt.2016.168DOI Listing

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