RRC ID 85653
著者 Masuda T, Watanabe T, Tatsumi Y, Lin J, Okumura K, Ozaki T, Sugiyama H, Kamikubo Y.
タイトル Cancer Accumulation and Anticancer Activity of "CROX (Cluster Regulation of RUNX)" PIP in HER2-Positive Gastric Cancer Evaluated by Chicken Egg Cancer Model.
ジャーナル Cancer Med
Abstract BACKGROUND:We have focused on pyrrole-imidazole (PI) polyamide compounds, which preferentially bind to their target DNA sequences. To validate our "CROX (Cluster Regulation of RUNX)" strategy, we have created a novel PI polyamide-based inhibitor against RUNX termed Chb-M'. Recently, we have confirmed its cancer-specific uptake in mouse xenograft derived from HER2-positive gastric cancer cells. The accumulation and efficacy of Chb-M' in cancer has not yet been investigated in vivo, which is a simpler and less expensive method other than mouse xenograft models.
METHODS:In the present study, we have employed the simple and versatile experimental system termed CAM (chorioallantoic membrane) model, and evaluated whether Chb-M' could have the cancer accumulation potential and anti-cancer activity.
RESULTS:Based on our present results, gastric cancer MKN45 cells transplanted onto CAM successfully developed cancers, and the intravenously injected FITC-labeled Chb-M' obviously accumulated in these CAM cancers. As expected, the treatment of the CAM cancers with Chb-M' significantly attenuated the growth of the CAM cancers. Our present results were basically identical to those obtained from mouse xenograft model.
CONCLUSION:Our present findings strongly suggest that Chb-M' preferentially accumulates in cancer to suppress its growth, and the CAM model might serve as a valuable and promising platform to rapidly assess the cancer uptake and anti-cancer efficacy of various PI polyamide-based drug candidates.
巻・号 14(7)
ページ e70845
公開日 2025-4-1
DOI 10.1002/cam4.70845
PMID 40171874
PMC PMC11962651
MeSH Animals Antineoplastic Agents* / pharmacology Cell Line, Tumor Cell Proliferation / drug effects Chickens Disease Models, Animal Humans Imidazoles* / chemistry Imidazoles* / pharmacology Mice Nylons* / chemistry Nylons* / pharmacology Pyrroles* / chemistry Pyrroles* / pharmacology Receptor, ErbB-2* / metabolism Stomach Neoplasms* / drug therapy Stomach Neoplasms* / genetics Stomach Neoplasms* / metabolism Stomach Neoplasms* / pathology Xenograft Model Antitumor Assays
IF 3.491
リソース情報
遺伝子材料 CS-RfA-ETV (RDB08020)