Esophageal squamous cell carcinoma (ESCC) is an upper gastrointestinal cancer with high morbidity and mortality. New strategies are urgently needed to prolong patients’ survival. Through screening FDA-approved drugs, we found dasabuvir, a drug approved for hepatitis C virus (HCV) treatment, suppressed ESCC proliferation. Dasabuvir could inhibit the growth of ESCC cells in a time and dose-dependent manner and arrested cell cycle at the G0/G1 phase. The antitumor activity was further validated in vivo using patient-derived xenograft tumor models. In terms of mechanism, we unveil that dasabuvir is a Rho-associated protein kinase 1 (ROCK1) inhibitor. Dasabuvir can bind to ROCK1 and suppress its kinase activity, thus downregulating the phosphorylation of ERK1/2 by ROCK1 and the expression of cyclin-dependent kinase 4 (CDK4) and cyclin D1. These results provide evidence that dasabuvir suppresses ESCC growth in vivo and in vitro through blocking ROCK1/ERK signaling pathway.
Gastrointestinal cancer represents a public health concern that seriously endangers human health. The emerging single-cell sequencing (SCS) technologies are different from the large-scale sequencing technologies which provide inaccurate data. SCS is a powerful tool for deciphering the single-cell resolutions of cellular and molecular landscapes, revealing the features of single-cell genomes, transcriptomes, and epigenomes. Recently, SCS has been applied in the field of gastrointestinal cancer research for clarifying the origin and heterogeneity of gastrointestinal cancer, acquiring micro-environmental information, and improving diagnostic and treatment methods. This review outlines the applications of SCS in gastrointestinal cancer research and summarizes the most recent advances in the field.
Esophageal squamous cell carcinoma (ESCC) is an upper gastrointestinal cancer with high morbidity and mortality. New strategies are urgently needed to prolong patients’ survival. Through screening of FDA-approved drugs, we found dasabuvir, a drug approved for hepatitis C virus (HCV) treatment, suppresses ESCC proliferation. Dasabuvir could inhibit the growth of ESCC cells in a time and dose-dependent manner and arrested cell cycle at the G0/G1 phase. The antitumor activity was further validated in vivo using a patient-derived xenograft tumor model in mice. In terms of mechanism, we unveiled that dasabuvir is a Rho-associated protein kinase 1 (ROCK1) inhibitor. Dasabuvir can bind to ROCK1 and suppress its kinase activity, thus downregulating phosphorylation of ERK1/2 by ROCK1 and expression of cyclin-dependent kinase 4 (CDK4) and cyclin D1. These results provide evidence that dasabuvir suppresses ESCC growth in vivo and in vitro through blocking ROCK1/ERK signaling pathway.
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