Emerging JWA-targeted Pt(IV) prodrugs conjugated with CX-4945 to overcome chemo-immune-resistance.

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ID: 71724
2019
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Ranked #22 of 66 articles by views in Biochemical and biophysical research communications

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Abstract
Two Pt(IV) prodrugs, Cx-platin-Cl and Cx-DN604-Cl, derived from the conjugation of cisplatin or DN604 with a CK2 inhibitor CX-4945, were constructed to suppress DNA damage repair-related elements. During in vitro biological studies, the Pt(IV) prodrugs had excellent cytotoxicity superior to cisplatin and DN604 to reverse drug resistance. Further mechanistic investigations revealed that the powerful anticancer activity of Cx-platin-Cl and Cx-DN604-Cl arisen from its suppression of JWA-XRCC1-mediated single-strand breaks repair. The emerging Pt(IV) prodrugs inhibited the growth of the xenografted tumors of C57BL6 and nude mice apart from JWA mice. Between them, Cx-platin-Cl augmented the infiltration and proliferation of T cells, alleviated the recruitment of T cells. The results provided compelling preclinical support that Cx-platin-Cl and Cx-DN604-Cl could reverse chemo-immune resistance via decaying JWA-XRCC1-mediated SSBR and immunosuppression, improving the development of emerging Pt(IV) candidate as a potential immunotherapeutic agent for cancer resistant prevention.
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chen2019emergingbiochemical Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Chen, Feihong;Pei, Sinan;Wang, Xing;Zhu, Qian;Gou, Shaohua;
Journal Biochemical and biophysical research communications
Year 2019
DOI
S0006-291X(19)32100-X
URL
Keywords
immunosuppression cisplatin resistance jwa-xrcc1 pt(iv) prodrug ssbr

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