Simultaneous inhibition of Chk1 and Bcl-xL induces apoptosis in vitro and represses tumour growth in an in vivo xenograft model

被引：0
|
作者：
Morimoto, Yoshihito [1 ]
Takada, Kimihiko [1 ]
Takeuchi, Osamu [2 ]
Watanabe, Kazuhiro [1 ]
Hirohara, Masayoshi [1 ]
Masuda, Yutaka [1 ]
机构：
[1] Showa Pharmaceut Univ, Ctr Educ & Res Clin Pharm, 3-3165 Higashi Tamagawagakuen, Machida, Tokyo 1948543, Japan
[2] Kitasato Inst Hosp, Dept Res, BioMed Lab, Tokyo, Japan
来源：
JOURNAL OF CHEMOTHERAPY | 2023年 / 35卷 / 05期
关键词：
Chk1; Bcl-2; Bcl-xL; Mcl-1; prexasertib; navitoclax; PANCREATIC-CANCER; CELL; COMBINATION; GEMCITABINE; NAVITOCLAX; RITUXIMAB; LEUKEMIA; VENETOCLAX; PHASE-2; S-1;
D O I：
10.1080/1120009X.2022.2125749
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
We previously showed that prexasertib, a checkpoint kinase 1 (Chk1) inhibitor, and navitoclax, a Bcl-2 and Bcl-xL inhibitor, induced a synergistic inhibitory effect on cell proliferation in vitro. Here, we investigated the effect of the simultaneous knockdown of Chk1 and each antiapoptotic protein of the Bcl-2 family (Bcl-2, Bcl-xL, or Mcl-1) with small interfering RNAs on apoptosis in three pancreatic cancer cell lines. Only simultaneous knockdown of Chk1 and Bcl-xL induced significant apoptosis compared with single knockdown in all three cell lines. We evaluated the anti-tumour effects of combined prexasertib and navitoclax treatment in a mouse xenograft model. Treatment to control volume ratios were calculated as 63.2% for prexasertib, 79.4% for navitoclax, and 36.8% for prexasertib and navitoclax. These findings suggest that the simultaneous inhibition of Chk1 and Bcl-xL may be an effective treatment for pancreatic cancer.
引用
收藏
页码：435 / 447
页数：13
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