High-Intensity Focused Ultrasound Enhanced Anti-Tumor Activities of Paclitaxel in Breast Cancer in vitro and in vivo.

Abstract

BackgroundPaclitaxel (PTX) is an important oncologic chemotherapeutic agent against breast cancer, but breast cancer patients develop significant resistance to PTX during chemotherapy. Alterations in tubulin and associated proteins have been implicated in resistance to PTX. High-intensity focused ultrasound (HIFU) induces deep tumor penetration of anti-tumor agents in solid tumors.MethodsWe investigated the influence of HIFU on the anti-tumor activities of PTX in breast cancer. Both in vivo and in vitro experiments were performed in this research: mice were treated with 2 mg/Kg PTX through tail vein injection, while breast cancer cells were treated with 400 nM PTX. Cell viability was analyzed through Cell Counting Kit-8. Cell apoptosis was evaluated through Annexin-V/PI Apoptosis Analysis Kit. The activities of catalase (CAT) and superoxide dismutase (SOD) and the concentration of malondialdehyde (MDA) were evaluated by relative commercial kits.ResultsHIFU enhanced PTX-inhibited breast cancer cell viability and PTX-induced cell apoptosis. Simultaneous treatment of HIFU and PTX decreased the activities of CAT and SOD and increased the concentration of MDA. In mice bearing MDA-MB-231 tumors, the treatment of HIFU and PTX significantly decreased tumor size, increased body weight and elevated animal survival. HIFU enhanced the distribution of PTX in tumor tissues.ConclusionThe performance of HIFU promoted the distribution of PTX and enhanced its anti-tumor activities in breast cancer.