G2 期检查点抑制剂 CBP-93872 可提高结直肠癌和胰腺癌细胞对化疗的敏感性。
The G2 checkpoint inhibitor CBP-93872 increases the sensitivity of colorectal and pancreatic cancer cells to chemotherapy.
作者信息
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
机构信息
Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan.
Department of Gastroenterological Surgery, Aichi Medical University School of Medicine, Nagakute, Japan.
出版信息
PLoS One. 2017 May 30;12(5):e0178221. doi: 10.1371/journal.pone.0178221. eCollection 2017.
CBP-93872 suppresses maintenance of DNA double-stranded break-induced G2 checkpoint, by inhibiting the pathway between ataxia-telangiectasia mutated (ATM) and ATM- and 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.
CBP-93872通过抑制共济失调毛细血管扩张症突变基因（ATM）与ATM及Rad3相关蛋白（ATR）激活之间的信号通路，抑制DNA双链断裂诱导的G2期检查点维持。为了研究CBP-93872在临床应用中的潜在用途，我们分析了含铂药物奥沙利铂和顺铂、嘧啶抗代谢物吉西他滨和5-氟尿嘧啶（5-FU）与CBP-93872联合使用对结直肠癌和胰腺癌细胞系细胞杀伤力的协同作用。用CBP-93872处理显著增加了癌细胞对通过抑制检查点激活所测试的各种化疗药物的敏感性。因此，我们的结果表明，CBP-93872与已知化疗药物联合治疗可抑制ATR和Chk1的磷酸化，并诱导细胞死亡。
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