ABT737, a Bcl2 family inhibitor, has a synergistic effect with apoptosis by inducing urothelial carcinoma cell necroptosis.

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Cheng R, Liu X, Wang Z, Tang K

ABT737, a Bcl2 family inhibitor, has a synergistic effect with apoptosis by inducing urothelial carcinoma cell necroptosis.

Mol Med Rep. 2021 Jun;23(6). pii: 412. doi: 10.3892/mmr.2021.12051. Epub 2021 Mar 31.

PubMed ID
33786632 [ View in PubMed
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Abstract

ABT737 is a recently reported inhibitor of members of the Bcl2 family of apoptosis regulators. However, to the best of our knowledge, its necroptosisinducing function in bladder cancer has not yet been researched. Thus, the present study aimed to investigate whether this Bcl2 family inhibitor can induce both apoptosis and necroptosis of urothelial carcinoma cells. The proliferation and survival of urothelial carcinoma cell lines treated with a combination of both ZVADFMK as a pancaspase inhibitor and ABT737 were assessed in vitro. ZDNA binding protein 1 (ZBP1), receptorinteracting protein (RIP)1 and RIP3 were knocked down using small interfering RNA in urothelial carcinoma cell lines. The protein expression levels of ZBP1, RIP1 and RIP3 following cell transfection were measured via western blot analysis. Cell viability was determined using an MTT assay. Cell invasion was examined using cell invasion assays. The expression levels of necroptosisrelated proteins, high mobility group box 1, ZBP1, mixedlineage kinase domainlike protein (MLKL) and RIP3, were measured via western blotting. It was found that ABT737 inhibited the proliferation and invasion of bladder cancer cells by inducing cell necrosis. The data demonstrated that ZBP1 and RIP3 have main roles in the cell necrosis induced by ABT737. In addition, RIP3 and ZBP1, without interacting with RIP1, directly induced MLKLmediated programmed cell necrosis. Thus, understanding how urothelial carcinoma cells react to Bcl2 family inhibitors may accelerate the discovery of drugs to treat bladder cancer.

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