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Article Abstract
Despite therapeutic advances, hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide. While dihydrotanshinone I (DHT) shows promising anticancer potential, its molecular mechanisms in HCC remain unexplored. Here, we unveil a novel chemokine (C-C motif) receptor 5 (CCR5)-mediated regulatory network targeted by DHT in HCC treatment. This study identifies CCR5 as a crucial survival factor in HCC, uncovers a novel CCR5-nuclear factor erythroid 2-related factor 2 (NRF2) regulatory axis, and reveals a dual-targeting mechanism of DHT through direct CCR5 inhibition and reactive oxygen species (ROS)-dependent cell death induction, validating its therapeutic efficacy by disrupting redox homeostasis. This work uncovers a novel CCR5-ROS-NRF2 signaling axis in HCC and establishes DHT as a promising therapeutic agent through its unique targeting mechanism. These findings provide new insights into HCC pathogenesis and present an innovative therapeutic strategy for HCC treatment.
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| http://dx.doi.org/10.1016/j.bcp.2025.117119 | DOI Listing |
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