[Effect of DR5-mediated Docetaxel-Loaded Lipid Microbubble Combined with Ultrasoundtargeted Microbubble Destruction on HepG2 Cell Proliferation and Apoptosis].

OBJECTIVE:To investigate the effect of DR5-mediated docetaxel-targeted lipid microbubbles (MBs) combined with ultrasound-targeted microbubble destruction on apoptosis and expressions of Bcl-2, nuclear factor-κB(NF-κB), caspase-8, and DR5 in human HepG2 cells.METHODS:HepG2 cells were treated with docetaxel at its 50% inhibitory concentration (IC50) of 5 nmol/L, docetaxel combined with ultrasound, blank MBs, blank MBs combined with ultrasound (0.5 W/cm2 for 45 s), drugloaded lipid MBs (DLLM), DLLM combined with ultrasound, DR5-mediated DLLM (DR5-DLLM), or DR5-DLLM combined with ultrasound.After the treatments, the cells were further cultured for 24 h, and CCK-8 assay, TUNEL staining and flow cytometry were used to assess cell proliferation, apoptosis, and cell cycle changes; the changes in mRNA and protein expression levels of Bcl-2, NF-κB, caspase-8, and DR5 were detected with RT-qPCR and Western blotting.RESULTS:Among all the treatments, DR5-DLLM combined with ultrasound produced the strongest effects to inhibit the proliferation (P < 0.001), promote apoptosis (P < 0.001), and cause G2/M cell cycle arrest (P < 0.001) in HepG2 cells.The combined treatment with DR5-DLLM and ultrasound also significantly downregulated Bcl-2 and NF-κB (P < 0.001) and upregulated DR5 and caspase-8 expressions (P < 0.001) at both the mRNA and protein levels.CONCLUSION:DR5-DLLM combined with ultrasound-targeted microbubble destruction can induce G2/M cell cycle arrest, proliferation inhibition and apoptosis in HepG2 cells by downregulating Bcl-2 and NF-κB and upregulating DR5 and caspase-8 expressions, indicating its value as a novel ultrasoundtargeted therapy for liver cancer.