Synergistic enhancement of cell death by triple combination therapy of docetaxel, ultrasound and microbubbles, and radiotherapy on PC3 a prostate cancer cell line

Almasri, Firas; Karshafian, Raffi

doi:10.1016/j.heliyon.2022.e10213

Cited by 2 publications

(1 citation statement)

References 62 publications

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“…This strategy may improve the therapeutic targeting of both the vascular and malignant compartments of a tumor. We have shown that the combination of the taxane, docetaxel (Taxotere, TXT), USMB, and XRT produced a synergistic enhancement of prostate-cancer-cell death in vitro [ 50 ]. We treated in vitro-suspended PC-3 prostate carcinoma cells with different combinations of XRT, TXT, and USMB.…”

Section: Introductionmentioning

confidence: 99%

Radioenhancement with the Combination of Docetaxel and Ultrasound Microbubbles: In Vivo Prostate Cancer

2023

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Using an in vitro prostate cancer model, we previously demonstrated the significant enhancement of radiotherapy (XRT) with the combined treatment of docetaxel (Taxotere; TXT) and ultrasound-microbubbles (USMB). Here, we extend these findings to an in vivo cancer model. Severe combined immune-deficient male mice were xenografted with the PC-3 prostate cancer cell line in the hind leg and treated with USMB, TXT, radiotherapy (XRT), and their combinations. The tumors were imaged with ultrasound pre-treatment and 24 h post-treatment, following which they were extracted for the histological analysis of the tumor-cell death (DN; H&E) and apoptosis (DA; TUNEL). The tumors’ growths were assessed for up to ~6 weeks and analysed using the exponential Malthusian tumor-growth model. The tumors’ doubling time (VT) was characterized as growth (positive) or shrinkage (negative). The cellular death and apoptosis increased ~5-fold with the TXT + USMB + XRT (Dn = 83% and Da = 71%) compared to the XRT alone (Dn = 16% and Da = 14%), and by ~2–3-fold with the TXT + XRT (Dn = 50% and Da = 38%) and USMB + XRT (Dn = 45% and Da = 27%) compared to the XRT. The USMB enhanced the cellular bioeffects of the TXT by ~2–5-fold with the TXT + USMB (Dn = 42% and Da = 50%), compared with the TXT alone (Dn = 19% and Da = 9%). The USMB alone caused cell death (Dn = 17% and Da = 10%) compared to the untreated control (Dn = 0.4% and Da = 0%). The histological cellular bioeffects were correlated with the changes in the ultrasound RF mid-band-fit data, which were associated with the cellular morphology. The linear regression analysis displayed a positive linear correlation between the mid-band fit and the overall cell death (R2 = 0.9164), as well as a positive linear correlation between the mid-band fit and the apoptosis (R2 = 0.8530). These results demonstrate a correlation between the histological and spectral measurements of the tissue microstructure and that cellular morphological changes can be detected by ultrasound scattering analysis. In addition, the tumor volumes from the triple-combination treatment were significantly smaller than those from the control, XRT, USMB + XRT, and TXT + XRT, from day 2 onward. The TXT + USMB + XRT-treated tumors shrank from day 2 and at each subsequent time-point measured (VT ~−6 days). The growth of the XRT-treated tumors was inhibited during the first 16 days, following which the tumors grew (VT ~9 days). The TXT + XRT and USMB + XRT groups displayed an initial decrease in tumor size (day 1–14; TXT + XRT VT ~−12 days; USMB + XRT VT ~−33 days), followed by a growth phase (day 15–37; TXT + XRT VT ~11 days; USMB + XRT VT ~22 days). The triple-combination therapy induced tumor shrinkage to a greater extent than any of the other treatments. This study demonstrates the in vivo radioenhancement potential of chemotherapy combined with therapeutic ultrasound-microbubble treatment in inducing cell death and apoptosis, as well as long-term tumor shrinkage.

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Section: Introductionmentioning

confidence: 99%

Radioenhancement with the Combination of Docetaxel and Ultrasound Microbubbles: In Vivo Prostate Cancer

2023

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Ultrasound‐stimulated microbubbles to enhance radiotherapy: A scoping review

McCorkell,

Piva,

Highgate

et al. 2024

J Med Imag Rad Onc

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IntroductionPrimarily used as ultrasound contrast agents, microbubbles have recently emerged as a versatile therapeutic vector that can be ‘burst’ to deliver payloads in the presence of suitably optimised ultrasound fields. Ultrasound‐stimulated microbubbles (USMB) have recently demonstrated improvements in treatment outcomes across a variety of clinical applications. This scoping review investigates whether this potential translates into the context of radiation therapy by evaluating the application of this technology across all three phases of radiation action.MethodsPrimary research articles, excluding poster presentations and conference proceedings, were identified through systematic searches of the PubMed NCBI/Medline, Embase/OVID, Web of Science and CINAHL/EBSCOhost databases, with additional articles identified via manual Google Scholar searching. Articles were dual screened for inclusion using the Covidence systematic review platform and classified against all three phases of radiation action.ResultsOverall, 57 eligible publications from a total of 1389 identified articles were included in the review, with studies dating back to 2012. Study heterogeneity prevented formal statistical analysis; however, most articles reported improved outcomes using USMB in the presence of radiation compared to that of radiation alone. These improvements appear to result from the use of USMB as either a biovascular disruptor causing tumour cell damage via indirect mechanisms, or as a localised treatment vector that directly increases tumour cell uptake of other therapeutic and physical agents designed to enhance radiation action.ConclusionsUSMB demonstrate exciting potential to enhance the effects of radiation treatments due to their versatility and capacity to target all three phases of radiation action.

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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

Cited by 2 publications

References 62 publications

Radioenhancement with the Combination of Docetaxel and Ultrasound Microbubbles: In Vivo Prostate Cancer

Radioenhancement with the Combination of Docetaxel and Ultrasound Microbubbles: In Vivo Prostate Cancer

Ultrasound‐stimulated microbubbles to enhance radiotherapy: A scoping review

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