AI Article Synopsis
- - This study explored the combined effects of a checkpoint kinase 1 (Chk1) inhibitor, prexasertib, and a Bcl-2 family inhibitor, navitoclax, on cell growth in pancreatic cancer.
- - Researchers found that knocking down both Chk1 and the anti-apoptotic protein Bcl-xL significantly increased cell death (apoptosis) in all tested pancreatic cancer cell lines, unlike the effects from single knockdowns.
- - In a mouse model, the combination treatment of prexasertib and navitoclax showed anti-tumor effects, suggesting that targeting both Chk1 and Bcl-xL might be a promising approach for pancreatic cancer therapy.
Article Abstract
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 . 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.
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| http://dx.doi.org/10.1080/1120009X.2022.2125749 | DOI Listing |
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Article Synopsis
- - This study explored the combined effects of a checkpoint kinase 1 (Chk1) inhibitor, prexasertib, and a Bcl-2 family inhibitor, navitoclax, on cell growth in pancreatic cancer.
- - Researchers found that knocking down both Chk1 and the anti-apoptotic protein Bcl-xL significantly increased cell death (apoptosis) in all tested pancreatic cancer cell lines, unlike the effects from single knockdowns.
- - In a mouse model, the combination treatment of prexasertib and navitoclax showed anti-tumor effects, suggesting that targeting both Chk1 and Bcl-xL might be a promising approach for pancreatic cancer therapy.
Chk1 Inhibition Potently Blocks STAT3 Tyrosine705 Phosphorylation, DNA-Binding Activity, and Activation of Downstream Targets in Human Multiple Myeloma Cells.
Mol Cancer Res
March 2022
Division of Hematology/Oncology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia.
Unlabelled: The relationship between the checkpoint kinase Chk1 and the STAT3 pathway was examined in multiple myeloma cells. Gene expression profiling of U266 cells exposed to low (nmol/L) Chk1 inhibitor [PF-477736 (PF)] concentrations revealed STAT3 pathway-related gene downregulation (e.g.
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