서강대학교

초록/요약

After conventional chemoradiotherapy, subpopulation of cancer cells remains senescence to become therapy resistance due to loss of proliferation. When such therapy induced senescence lung cancer cells (TISLC) escape from senescence to regrow, highly aggressive growth potential can be acquired to result in cancer relapse. Thus, small molecules to induce selective cell death of senescent cancer cells (cancer senolytics) have been studied. Using public data, we predicted cancer senolytic compound “ABT-263”, which was BH3 mimetics, and validated. Following other BH3 mimetics experiments revealed that senolytic effect of ABT-263 was independent with BCL2 family. Thorough transcriptome analysis of senescent lung cancer cell model, induced either by ionizing radiation or bleomycin, we found that Wnt gene signature was highly enriched in TISLC. Following biochemical study confirmed that Wnt activity, determined by Wnt reporter and level of active -catenin, was significantly increased in TISLC, suggesting an important role of Wnt activity in survival of TISLC. As well as we found that Wnt activity after treatment ABT-263 in TISLC decreased. It suggests that Wnt activity in senescent cancer cells is critical for maintaining survival and would be a promising target for cancer senolytics.