Synergistic effects of sonoporation and taurolidin/TRAIL on apoptosis in human fibrosarcoma.
Sonodynamic therapy, in combination with ultrasound contrast agents, proved to enhance the uptake of chemotherapeutics in malignant cells. HT1080 fibrosarcoma cells were treated in vitro with a combination of ultrasound SonoVue™-microbubbles and taurolidine (TRD) plus tumor necrosis factor related apoptosis inducing ligand (TRAIL). Apoptosis was measured by TdT-mediated dUTP-biotin nick end labelling (TUNEL) assay and fluorescence activated cell sorting (FACS) analysis. Gene expression was analysed by RNA-microarray. The apoptotic effects of TRD and TRAIL on human fibrosarcoma are enhanced by sonodynamic therapy and additional application of contrast agents, such as SonoVue™ by 25%. A broad change in the expression of genes related to apoptotic pathways is observed when ultrasound and microbubbles act synchronously in combination with the chemotherapeutics (e.g. BIRC3, NFKBIA and TNFAIP3). Some of these genes have already been proven to play a role in programmed cell death in human fibrosarcoma (HSPA1A/HSPA1B, APAF1, PAWR, SOCS2) or were associated with sonication induced apoptosis (CD44). Further studies are needed to explore the options of sonodynamic therapy on soft tissue sarcoma and its molecular mechanisms.
Daigeler
Adrien
A
Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG-Unfallkrankenhaus, Ludwigshafen, Germany. adaigeler@bgu-ludwigshafen.de
Chromik
Ansgar M
AM
Haendschke
Kathrin
K
Emmelmann
Sabine
S
Siepmann
Monica
M
Hensel
Karin
K
Schmitz
Georg
G
Klein-Hitpass
Ludger
L
Steinau
Hans U
HU
Lehnhardt
Marcus
M
Hauser
Joerg
J
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects; D003287:Contrast Media / Q000494:pharmacology; D005354:Fibrosarcoma / Q000628:therapy*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020287:In Situ Nick-End Labeling; D020411:Oligonucleotide Array Sequence Analysis; D010743:Phospholipids / Q000494:pharmacology*; D012983:Soft Tissue Neoplasms / Q000628:therapy*; D013459:Sulfur Hexafluoride / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013829:Thiadiazines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014464:Ultrasonic Therapy / Q000379:methods*
D003287:Contrast Media; D010743:Phospholipids; D053221:TNF-Related Apoptosis-Inducing Ligand; D013829:Thiadiazines; C420843:contrast agent BR1; D013654:Taurine; C012566:taurolidine; D013459:Sulfur Hexafluoride