Ultrasound Amplification Of Tumor Cell Biomarkers Experimental Study And Mechanism Of Action

Serum Tumor marker (TM) detection has been widely used in the early diagnosis of ovarian cancer, however its levels are extremely low in early cancer patients, and a range of other non-cancer factors (ascites, inflammation, endometrial ectopic psychosis) may cause abnormal raise of TM, making it extremely difficult to detect early sign of ovarian cancer.Therefore, we use ultrasound to study the biological effects, by first raising TMs concentration after sonication, then analyze ultrasonic parameters that cause increase of TM. We focused on the establishment of models of ultrasounic amplification on cells and mouse xenograft and its application in early detection of ovarian cancer.In this paper, research is divided into the following several aspects:1. At ultrasonic frequency of 1MHz (0.1 W/cm2?0.3 W/cm2,1 min?5 min), TMs concentration (CA125, CA199) were detected in the cell supernatant by Electrochemiluminescence immunoassay (ECLIA). Considering TMs increment and ultrasonic energy level as the main investigation indexes, we optimized ultrasonic parameters combination to get the goal of large increment of more markers, established the relationship between the dose of ultrasonic energy and increments of markers. Based on the model of mouse xenograft, experiments were carried out to verify the feasibility of ultrasounic amplification of TMs.2. Sonication to epithelial ovarian cancer cells (SKOV3) by using a self made 1 MHz ultrasound generator, trypan blue staining, Edu cell proliferation assay, MTT proliferation test, Transwell invasion assay were used to detect the ultrasonic effects of ovarian cancer cells mortality, proliferation and invasion. Immunohistochemistry were performed on tumor E-cadherin, vimentin staining after sonication on ovarian cancer xenograft tumor model.3. In this paper, no significant damages were observed after sonication in vitro and in vivo by using a low-power ultrasound (below the US Food and Drug Administration requirements). The method of TM amplification by ultrasound is safe and reliable.