title: High intensity focused ultrasound-induced gene activation in sublethally injured tumor cells in vitro.
abstract: Cultured human cervical cancer (HeLa) and rat mammary carcinoma (R3230Ac) cells were transfected with vectors encoding green fluorescent protein (GFP) under the control of hsp70B promoter. Aliquots of 10-microl transfected cells (5 x 10(7) cells/ml) were placed in 0.2-ml thin-wall polymerase chain reaction tubes and exposed to 1.1-MHz high intensity focused ultrasound (HIFU) at a peak negative pressure P- = 2.68 MPa. By adjusting the duty cycle of the HIFU transducer, the cell suspensions were heated to a peak temperature from 50 to 70 degrees C in 1-10 s. Exposure dependent cell viability and gene activation were evaluated. For a 5-s HIFU exposure, cell viability dropped from 95% at 50 degrees C to 13% at 70 degrees C. Concomitantly, gene activation in sublethally injured tumor cells increased from 4% at 50 degrees C to 41% at 70 degrees C. A similar trend was observed at 60 degrees C peak temperature as the exposure time increased from 1 to 5 s. Further increase of exposure duration to 10 s led to significantly reduced cell viability and lower overall gene activation in exposed cells. Altogether, maximum HIFU-induced gene activation was achieved at 60 degrees C in 5 s. Under these experimental conditions, HIFU-induced gene activation was found to be produced primarily by thermal rather than mechanical stresses.
authors.affiliation: Department of Mechanical Engineering and Materials Science, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Liu
authors.forename: Takashi
authors.initials: T
authors.lastname: Kon
authors.forename: Chuanyuan
authors.initials: C
authors.lastname: Li
authors.forename: Pei
authors.initials: P
authors.lastname: Zhong
mesh_terms: D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D018869:Heat-Shock Response; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D013314:Stress, Mechanical; D015533:Transcriptional Activation; D014464:Ultrasonic Therapy; D014463:Ultrasonography