Target tumor therapy in human gastric cancer cells through the combination of docetaxel-loaded cationic lipid microbubbles and ultrasound-triggered microbubble destruction

Abstract

It is well accepted that ultrasound-induced microbubble (USMB) cavitation is a promising method for drug delivery. Ultrasound-targeted destruction of cytotoxic drug-loaded lipid microbubbles (LMs) is used to promote the treatment of cancer. This study aimed to investigate the antitumor effects from a combination of docetaxel-loaded cationic lipid microbubbles (DLLM⁺) and ultrasound (US)-triggered microbubble destruction (UTMD) on gastric cancer (GC). It was found that the functional dose of DOC in this study was 1 × 10^-9 mol/L. We found that DLLM combined with the UTMD group showed greater growth inhibition of the cultured human gastric cancer cells (HGCCs) when compared with the other five groups by arresting the G₂/M phase in the cell cycle. However, DLLM⁺ combined with UTMD showed a higher inhibition rate of tumor growth than DLLM combined with UTMD and that of the RC/CMV-p16 combined with UTMD in vitro and in vivo experiments. DLLM⁺ combined with UTMD significantly suppressed proliferation and promoted the apoptosis of HGCCs with more cells arrested in the G₂/M phase. In addition, DLLM⁺ combined with UTMD suppressed the proliferation and induced apoptosis by arresting cells in the G₂/M phase, which led to a great inhibition of GC progression. Thus, our results indicated that the combination of DLLM⁺ and UTMD might represent a novel and promising approach to chemotherapy for GC.

Keywords: Cationic lipid microbubbles; Docetaxel; Gastric cancer; Ultrasound.