Enhanced Proliferation Inhibition and Apoptosis-Inducing Effects of Docetaxel-Loaded Lipid Microbubble on Human Pancreatic Cancer Cells in Vitro

OBJECTIVE:To investigate the proliferation inhibition and apoptosis-inducing effect of docetaxel-loaded lipid microbubble (DLLM) combined with ultrasound targeted microbubble destruction (UTMD) on human pancreatic cancer cells in vitro.METHODS:DLLM was prepared by mechanical vibration, and its physical properties were characterized. The median inhibitory concentration (IC(50)) of DLLM was determined with MTT assay, and its cytotoxicity evaluated with cell counting Kit-8 (CCK-8) assay. The effects of docetaxel, DLLM, and DLLM combined with UTMD on cell cycle and apoptosis of BxPC3 cells were tested with flow cytometry (FCM) and TUNEL assay, respectively.RESULTS:DLLM had an average size of 1.6 µm, and the average drug entrapment efficiency and drug-loaded amount was 64.2% and 16.1%, respectively. Compared with the control groups, DLLM had a significantly enhanced cytotoxic effect (P<0.01) and caused an increased apoptosis rate in BxPC3 cells (P<0.01). Cell cycle analysis showed that DLLM combined with UTMD resulted in an significantly higher percentage of cells with G(2)/M phase arrest than the other treatments (P<0.01).CONCLUSIONS:DLLM combined with UTMD can increase G(2)/M phase arrest and enhance the proliferation inhibition and apoptosis-inducing effect on BxPC3 cells, and can serve as an effective drug delivery system for pancreatic cancer therapy.