The G2 checkpoint inhibitor CBP-93872 increases the sensitivity of colorectal and pancreatic cancer cells to chemotherapy

作者：Iwata Tsutomu; Uchino Tairin; Koyama Ayako; Johmura Yoshikazu; Koyama Kenichi; Saito Takuya; Ishiguro Seiji; Arikawa Takashi; Komatsu Shunichiro; Miyachi Masahiko; Sano Tsuyoshi; Nakanishi Makoto; Shimada Midori^*

来源：PLos One, 2017, 12(5): e0178221.

DOI：10.1371/journal.pone.0178221

CBP-93872 suppresses maintenance of DNA double-stranded break-induced G2 checkpoint, by inhibiting the pathway between ataxia-telangiectasia mutated (ATM) and ATMand Rad3-related (ATR) activation. To examine the potential use of CBP-93872 for clinical applications, we analyzed the synergistic effects of platinum-containing drugs, oxaliplatin and cisplatin, pyrimidine antimetabolites, gemcitabine and 5-fluorouracil (5-FU), in combination with CBP-93872, on cell lethality in colorectal and pancreatic cancer cell lines. Treatment with CBP-93872 significantly increased cancer cell sensitivities to various chemotherapeutic agents tested through suppression of checkpoint activation. Our results thus reveal that combination treatment of CBP-93872 with known chemotherapeutic agents inhibits phosphorylation of ATR and Chk1, and induces cell death.

• 出版日期2017-5-30
• 单位河北医科大学