KLF5 inhibition overcomes oxaliplatin resistance in patient-derived colorectal cancer organoids by restoring apoptotic response

• DOI: 10.1038/s41419-022-04773-1
• Publication Date: 2022-04-05T03:45:29Z
• Authors: Xiaohui Shen; Yuchen Zhang; Zhuoqing Xu; Han Gao; Wenqing Feng; Wenchang Li; Yiming Miao; Zifeng Xu; Yaping Zong; Jingkun Zhao; Aiguo Lu
• Keywords: Organoid

Abstract Oxaliplatin resistance is a major challenge in the treatment of colorectal cancer (CRC). Many molecular targeted drugs for refractory CRC have been developed to solve drug resistance, but their effectiveness and roles progression oxaliplatin remain unclear. Here, we successfully constructed PDOs selected Kruppel-like factor 5 (KLF5) inhibitor ML264 as research object based on results vitro screening assay. significantly restored sensitivity by restoring apoptotic response, this effect was achieved inhibiting KLF5/Bcl-2/caspase3 signaling pathway. Chromatin immunoprecipitation (ChIP) luciferase reporter assays verified that KLF5 promoted transcription Bcl-2 cells. inhibition also overcame xenograft tumors. Taken together, our study demonstrated can restore response. may be potential therapeutic target oxaliplatin-resistant CRC. strong evaluating inhibitors combination therapy preclinical environment.