Cargando…

A 3D culture system for evaluating the combined effects of cisplatin and anti-fibrotic drugs on the growth and invasion of lung cancer cells co-cultured with fibroblasts

Fibrosis and fibroblast activation usually occur in the tissues surrounding a malignant tumor; therefore, anti-fibrotic drugs are used in addition to chemotherapy. A reliable technique for evaluating the combined effects of anti-fibrotic drugs and anticancer drugs would be beneficial for the develop...

Descripción completa

Detalles Bibliográficos
Autores principales: Pan, Huei-Jyuan, Lee, Chia-Wei, Wu, Li-Yu, Hsu, Heng-Hua, Tung, Yi-Chung, Liao, Wei-Yu, Lee, Chau-Hwang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AIP Publishing LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060027/
https://www.ncbi.nlm.nih.gov/pubmed/37006781
http://dx.doi.org/10.1063/5.0115464
_version_ 1785017018213203968
author Pan, Huei-Jyuan
Lee, Chia-Wei
Wu, Li-Yu
Hsu, Heng-Hua
Tung, Yi-Chung
Liao, Wei-Yu
Lee, Chau-Hwang
author_facet Pan, Huei-Jyuan
Lee, Chia-Wei
Wu, Li-Yu
Hsu, Heng-Hua
Tung, Yi-Chung
Liao, Wei-Yu
Lee, Chau-Hwang
author_sort Pan, Huei-Jyuan
collection PubMed
description Fibrosis and fibroblast activation usually occur in the tissues surrounding a malignant tumor; therefore, anti-fibrotic drugs are used in addition to chemotherapy. A reliable technique for evaluating the combined effects of anti-fibrotic drugs and anticancer drugs would be beneficial for the development of an appropriate treatment strategy. In this study, we manufactured a three-dimensional (3D) co-culture system of fibroblasts and lung cancer cell spheroids in Matrigel supplemented with fibrin (fibrin/Matrigel) that simulated the tissue microenvironment around a solid tumor. We compared the efficacy of an anticancer drug (cisplatin) with or without pretreatments of two anti-fibrotic drugs, nintedanib and pirfenidone, on the growth and invasion of cancer cells co-cultured with fibroblasts. The results showed that the addition of nintedanib improved cisplatin's effects on suppressing the growth of cancer cell spheroids and the invasion of cancer cells. In contrast, pirfenidone did not enhance the anticancer activity of cisplatin. Nintedanib also showed higher efficacy than pirfenidone in reducing the expression of four genes in fibroblasts associated with cell adhesion, invasion, and extracellular matrix degradation. This study demonstrated that the 3D co-cultures in fibrin/Matrigel would be useful for assessing the effects of drug combinations on tumor growth and invasion.
format Online
Article
Text
id pubmed-10060027
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher AIP Publishing LLC
record_format MEDLINE/PubMed
spelling pubmed-100600272023-03-30 A 3D culture system for evaluating the combined effects of cisplatin and anti-fibrotic drugs on the growth and invasion of lung cancer cells co-cultured with fibroblasts Pan, Huei-Jyuan Lee, Chia-Wei Wu, Li-Yu Hsu, Heng-Hua Tung, Yi-Chung Liao, Wei-Yu Lee, Chau-Hwang APL Bioeng Articles Fibrosis and fibroblast activation usually occur in the tissues surrounding a malignant tumor; therefore, anti-fibrotic drugs are used in addition to chemotherapy. A reliable technique for evaluating the combined effects of anti-fibrotic drugs and anticancer drugs would be beneficial for the development of an appropriate treatment strategy. In this study, we manufactured a three-dimensional (3D) co-culture system of fibroblasts and lung cancer cell spheroids in Matrigel supplemented with fibrin (fibrin/Matrigel) that simulated the tissue microenvironment around a solid tumor. We compared the efficacy of an anticancer drug (cisplatin) with or without pretreatments of two anti-fibrotic drugs, nintedanib and pirfenidone, on the growth and invasion of cancer cells co-cultured with fibroblasts. The results showed that the addition of nintedanib improved cisplatin's effects on suppressing the growth of cancer cell spheroids and the invasion of cancer cells. In contrast, pirfenidone did not enhance the anticancer activity of cisplatin. Nintedanib also showed higher efficacy than pirfenidone in reducing the expression of four genes in fibroblasts associated with cell adhesion, invasion, and extracellular matrix degradation. This study demonstrated that the 3D co-cultures in fibrin/Matrigel would be useful for assessing the effects of drug combinations on tumor growth and invasion. AIP Publishing LLC 2023-03-28 /pmc/articles/PMC10060027/ /pubmed/37006781 http://dx.doi.org/10.1063/5.0115464 Text en © 2023 Author(s). https://creativecommons.org/licenses/by/4.0/All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Articles
Pan, Huei-Jyuan
Lee, Chia-Wei
Wu, Li-Yu
Hsu, Heng-Hua
Tung, Yi-Chung
Liao, Wei-Yu
Lee, Chau-Hwang
A 3D culture system for evaluating the combined effects of cisplatin and anti-fibrotic drugs on the growth and invasion of lung cancer cells co-cultured with fibroblasts
title A 3D culture system for evaluating the combined effects of cisplatin and anti-fibrotic drugs on the growth and invasion of lung cancer cells co-cultured with fibroblasts
title_full A 3D culture system for evaluating the combined effects of cisplatin and anti-fibrotic drugs on the growth and invasion of lung cancer cells co-cultured with fibroblasts
title_fullStr A 3D culture system for evaluating the combined effects of cisplatin and anti-fibrotic drugs on the growth and invasion of lung cancer cells co-cultured with fibroblasts
title_full_unstemmed A 3D culture system for evaluating the combined effects of cisplatin and anti-fibrotic drugs on the growth and invasion of lung cancer cells co-cultured with fibroblasts
title_short A 3D culture system for evaluating the combined effects of cisplatin and anti-fibrotic drugs on the growth and invasion of lung cancer cells co-cultured with fibroblasts
title_sort 3d culture system for evaluating the combined effects of cisplatin and anti-fibrotic drugs on the growth and invasion of lung cancer cells co-cultured with fibroblasts
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060027/
https://www.ncbi.nlm.nih.gov/pubmed/37006781
http://dx.doi.org/10.1063/5.0115464
work_keys_str_mv AT panhueijyuan a3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT leechiawei a3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT wuliyu a3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT hsuhenghua a3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT tungyichung a3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT liaoweiyu a3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT leechauhwang a3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT panhueijyuan 3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT leechiawei 3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT wuliyu 3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT hsuhenghua 3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT tungyichung 3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT liaoweiyu 3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts
AT leechauhwang 3dculturesystemforevaluatingthecombinedeffectsofcisplatinandantifibroticdrugsonthegrowthandinvasionoflungcancercellscoculturedwithfibroblasts