| Summary: | 碩士 === 國立臺灣大學 === 生化科學研究所 === 107 === Lung cancer has a high mortality rate and often metastasizes to other organs. The cell line used in the study was CL1-5, which is a non-small cell lung cancer (NSCLC). According to previous studies, cancer cells can be killed through blocking the interaction between CCT-β and β-tubulin by I-Trp. The small molecule compound-845 used in this study was screened among a series of bactericidal compounds synthesized by NHRI and is the most potential to kill CL1-5 cells. In addition, its structure is composed of a functional group which is similar to the reversible inhibitors of CCT-β: β-tubulin complex previously simulated by computer and a side chain of I-Trp. It has been found that compound-845 would induce ER stress in CL1-5 cells, which in turn leads to the release of intracellular calcium ion and apoptosis. Furthermore, analyzed by wound healing assay and transwell assay, it has been found that compound-845 would inhibit the migratory and invasive ability of CL1-5 cells. Moreover, compound-845 would inhibit EMT, AKT/β-catenin and integrin signaling pathway investigated by western blot, thereby inhibiting CL1-5 cell metastasis.
In conclusion, this study reveals that this dual-functional inhibitor compound-845 probably has anti-tumor and anti-metastasis ability against human lung cancer.
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