Effects of high-intensity focused ultrasound on cisplatin-resistant human lung adenocarcinoma in vitro and in vivo

It is widely accepted that high-intensity focused ultrasound （HIFU） is a minimally invasive treatment option for different tumors, but its roles and the corresponding mechanism in cisplatin （DDP） che- moresistance in lung adenocarcinoma （LA） remain unclear. In this study, we investigated the response of DDP-resistant LA cells to HIFU and its underlying molecular mechanisms using molecu- lar biology techniques. It was found that HIFU exposure inhibited the proliferation of DDP-resistant A549 （A549/DDP） cells through arresting cell cycle at the G1/G0 phase via the Cyclin-dependent path- way and promoting apoptosis in a Bcl-2-dependent manner. Furthermore, the results also showed that HIFU exposure could down-regulate the expressions of MDR1, MRP1, and LRP mRNAs, as well as P-gp, MRP1, and LRP proteins related to drug resistance in A549/DDP cells. In vivo experiments also demonstrated that HIFU could reduce the size and mass of subcutaneously transplanted tumors produced by A549/DDP cells through mediating Cycin-dependent and Bcl-2-dependent pathways. These results suggested that HIFU treatment could inhibit the proliferation of DDP-resistant lung cancer cells and might be a novel therapeutic method for patients with DDP resistance.