Abstract 1568
Background
In order to improve the efficacy of chemotherapy an increasing attention is given to the drug transport to tumors. Sonoporation is the application of ultrasound (US) to increase cell membrane permeability. It is thought that US induces expansion, contraction, and explosion of microbubbles (MB) thus creating pores in the cell membrane, enhancing drug delivery and efficacy. It is important to investigate this phenomenon not only into monolayer cultured cells but also into cell spheroids that imitate the biological characteristics of tumor better than 2D cell cultures. The aim of our study was to evaluate the influence of US on the efficacy of three anticancer drugs doxorubicin (DOX), 5-fluorouracil (5-FU) and paclitaxel (PTX) into 2D and 3D A549 non-small cell lung cancer cell cultures.
Methods
US pulse repetition frequency of 10 Hz and 1 MHz center frequency were generated with peak negative pressure of 0.5 MPa and 50% duty cycle. SonoVue™ MB were used. The effect of DOX on cell viability was tested by MTT assay. Spheroids were formed using 3D Bioprinting method mixing A549 cells with human fibroblasts. DOX delivery in 2D and 3D cultures was assessed using fluorescence microscopy. DOX toxicity in tumor spheroids was evaluated according to the change of spheroid size.
Results
Separately applied US and MB did not increase DOX cytotoxicity. Meanwhile, the combination of US and MB increased DOX efficacy by approximately 4% when compared to DOX alone. US exposure did not show a positive effect on DOX delivery in 2D cancer cell cultures. On the other hand, US increased DOX delivery in tumor spheroids. 15 sec. of US exposure increased DOX penetration in the edge and middle zones of spheroids from 12 to 60%. 2 min. of US exposure decreased the amount of DOX in these zones. US also increased DOX, 5-FU and PTX toxicity in cancer cell spheroids 8-, 1.2- and 1.5-fold, respectively.
Conclusions
US is a promising physical method to enhance anticancer drug efficacy, especially into 3D cell cultures. However, there is a lack of evidence about its efficacy and further studies are needed.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Lithuanian University of Health Sciences; Kaunas University of Technology.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2728 - MicroRNA expression and DNA methylation profiles do not distinguish between primary and recurrent well-differentiated liposarcoma
Presenter: Melissa Vos
Session: Poster Display session 1
Resources:
Abstract
3197 - Genomic Alterations, Tumor Mutation Burden and Prognosis of Chinese Cardiac Sarcoma Patients
Presenter: Na Zhu
Session: Poster Display session 1
Resources:
Abstract
4214 - Evaluation of a peptide-conjugated alkylator melflufen in osteosarcoma preclinical models
Presenter: Konstantin Byrgazov
Session: Poster Display session 1
Resources:
Abstract
2654 - Expression analysis of NHEJ and HR genes in Ewing sarcomas: indications of DSB repair dysfunction
Presenter: Anastasios Kyriazoglou
Session: Poster Display session 1
Resources:
Abstract
4383 - Epidemiology of Synovial Sarcoma in EU28 countries
Presenter: Nedra Joseph
Session: Poster Display session 1
Resources:
Abstract
1937 - Resection Of High-Grade Large Soft Tissue Sarcoma With Adequate Wide Margin Can Lead To Good Local Control Without Adjuvant Radiotherapy
Presenter: Toshiyuki Kunisada
Session: Poster Display session 1
Resources:
Abstract
3757 - Influence of eribulin on proliferation, migration and invasion properties of leiomyosarcoma cell line models
Presenter: Marta Mendiola
Session: Poster Display session 1
Resources:
Abstract
1040 - EREMISS: Efficacy of regorafenib (REG) as maintenance therapy in non-adipocytic soft tissue sarcomas (STS) having received 1st-line doxorubicin-based chemotherapy (Doxo-CT)
Presenter: Nicolas Penel
Session: Poster Display session 1
Resources:
Abstract
1048 - A Phase 2 biomarker-driven study evaluating the clinical efficacy of an MDM2 inhibitor, milademetan, in patients with intimal sarcoma, a disease with a high unmet need
Presenter: Kan Yonemori
Session: Poster Display session 1
Resources:
Abstract
1511 - A pilot study of oral paclitaxel (ORAXOL) in subjects with cutaneous angiosarcomas (KX-ORAX-010)
Presenter: Herbert Loong
Session: Poster Display session 1
Resources:
Abstract