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
2304 - Synthetic peptide of tumor–associated antigen L6 formulated with polymer-based adjuvant enhances anti-tumor effects in mice
Presenter: Shih-jen Liu
Session: Poster Display session 1
Resources:
Abstract
4419 - Improving detection level of somatic mosaicism in neurofibromatosis type 1
Presenter: Kristina Karandasheva
Session: Poster Display session 1
Resources:
Abstract
5283 - Preclinical pharmacokinetic/pharmacodynamic (PK/PD) relationship of ABN401, a highly selective Met inhibitor, in gastric and non-small-cell lung cancer models
Presenter: JooSeok Kim
Session: Poster Display session 1
Resources:
Abstract
5488 - Transcription factors of Snail family in the regulation of resistance of breast cancer cells to hypoxic conditions
Presenter: Alvina Khamidullina
Session: Poster Display session 1
Resources:
Abstract
5417 - Metastasis is impaired by endothelial-specific Dll4 loss-of-function through inhibition of epithelial-to-mesenchymal transition and reduction of cancer stem cells and circulating tumour cells
Presenter: Liliana Mendonça
Session: Poster Display session 1
Resources:
Abstract
5494 - Identification of novel and known FGFR gene fusions in Chinese non-small cell lung cancer
Presenter: Weixin Zhao
Session: Poster Display session 1
Resources:
Abstract
3412 - WNT pathway mutations (APC/CTNNB1) and immune checkpoint inhibitors (ICI) response in metastatic non-small cell lung cancer (NSCLC) patients.
Presenter: Francisco Javier Ros Montana
Session: Poster Display session 1
Resources:
Abstract
1815 - Leukocytosis as a negative prognostic factor in patients with lung cancer: Which subpopulation of leukocytes is responsible?
Presenter: Filip Kohutek
Session: Poster Display session 1
Resources:
Abstract
5022 - Identification of MET gene amplifications using next-generation sequencing in non-small cell lung cancer patients
Presenter: Sergi Clavé
Session: Poster Display session 1
Resources:
Abstract
4925 - Prognostic role of CD73 in metastatic Non Small Cell Lung Cancer according to the presence of driver alterations
Presenter: Giulia Galli
Session: Poster Display session 1
Resources:
Abstract