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Synergistic enhancement of cell death by triple combination therapy of docetaxel, ultrasound and microbubbles, and radiotherapy on PC3 a prostate cancer cell line
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Almasri, Firas and Karshafian, Raffi (2022) Synergistic enhancement of cell death by triple combination therapy of docetaxel, ultrasound and microbubbles, and radiotherapy on PC3 a prostate cancer cell line. Heliyon, 8 (8). e10213. doi:10.1016/j.heliyon.2022.e10213 ISSN 2405-8440.
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WRAP-synergistic-enhancement-cell-death-triple-combination-therapy-docetaxel-ultrasound-microbubbles-radiotherapy-PC3-prostate-cancer-cell-line-Almasri-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (3546Kb) | Preview |
Official URL: http://dx.doi.org/10.1016/j.heliyon.2022.e10213
Abstract
The application of ultrasound and microbubbles (USMB) has been shown to enhance both chemotherapy and radiotherapy. This study investigated the potential of triple combination therapy comprised of USMB, docetaxel (Taxotere: TXT) chemotherapy and XRT to enhance treatment efficacy. Prostate cancer (PC3) cells in suspension were treated with various combinations of USMB, chemotherapy and radiotherapy. Cells were treated with ultrasound and microbubbles (500 kHz pulse center frequency, 580 kPa peak negative pressure, 10 μs pulse duration, 60 s insonation time and 2% Definity microbubbles (v/v)), XRT (2 Gy), and Taxotere (TXT) at concentrations ranging from 0.001 to 0.1 nM for 5- and 120-minutes duration. Following treatment, cell viability was assessed using a clonogenic assay. Therapeutic efficiency of the combined treatments depended on chemotherapy and microbubble exposure conditions. Under the exposure conditions of the study, the triple combination therapy synergistically enhanced clonogenic cell death compared to single and double combination therapy. Cell viability of ∼2% was achieved with the triple combination therapy corresponding to ∼29, ∼37, and ∼38 folds decrease compared to XRT (57%), USMB (74%) and TXT (76%) alone conditions, respectively. In addition, the triple combination therapy decreased cell viability by ∼29, ∼19- and ∼11 folds compared to TXT2hr + USMB (58%), TXT2hr + XRT (37%), and USMB + XRT (22%), respectively.
The in vivo PC3 tumours showed that USMB significantly enhanced cell death through detection of apoptosis (TUNEL) with both TXT and TXT + XRT. The study demonstrated that the triple combination therapy can significantly enhance cell death in prostate cancer cells both in vitro and in vivo under relatively low chemotherapy and ionizing radiation doses.
Item Type: | Journal Article | ||||||||
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Subjects: | R Medicine > RM Therapeutics. Pharmacology | ||||||||
Divisions: | Faculty of Social Sciences > Centre for Education Studies (2013- ) | ||||||||
Library of Congress Subject Headings (LCSH): | Chemotherapy, Ultrasonic waves -- Therapeutic use , Ultrasonics in medicine, Microbubbles, Radiotherapy | ||||||||
Journal or Publication Title: | Heliyon | ||||||||
Publisher: | Elsevier | ||||||||
ISSN: | 2405-8440 | ||||||||
Official Date: | August 2022 | ||||||||
Dates: |
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Volume: | 8 | ||||||||
Number: | 8 | ||||||||
Article Number: | e10213 | ||||||||
DOI: | 10.1016/j.heliyon.2022.e10213 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 17 October 2022 | ||||||||
Date of first compliant Open Access: | 18 October 2022 | ||||||||
RIOXX Funder/Project Grant: |
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