Comparison of the apoptotic effects of bortezomib using 2D and 3D co-culture models of THP-1 derived macrophage and A549 lung cancer

Miriş Dikmen; Zerrin Cantürk

Makale detayları

Comparison of the apoptotic effects of bortezomib using 2D and 3D co-culture models of THP-1 derived macrophage and A549 lung cancer

Yazarlar:

Miriş Dikmen | Zerrin Cantürk

Yayıncı:

Marmara University

Ana Başlıklar:

Basic Pharmacology | Medical Pharmacology

Dergi:

Journal of Research in Pharmacy Vol.25 Issue 4, pp.490-499

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001348088

pISSN:

2630-6344

Anahtar kelimeler:

Özet:

 We investigated the fundamental function of the lung cancer tumour microenvironment. Proteasome inhibition has emerged as a clinically successful anti-cancer therapeutic strategy, with the antineoplastic medication bortezomib showing high efficacy against multiple cancers. Tumour-associated macrophages TAMs, which migrate to tumour stroma, are known to promote cell proliferation, apoptosis, and metastasis within the lung cancer microenvironment. However, the specific interaction of macrophages, lung cancer cells, and bortezomib are still unclear. Most in vitro cell cultures are traditionally grown in a two-dimensional 2D culture system, although 3D cultures have demonstrated greater success in terms of drug response, gene expression and viability. Therefore, to elucidate the role of macrophages, we aimed to establish a co-culture model in both 2D and 3D cultures using A549 human lung cancer cells and THP-1 derived macrophages. Apoptotic effects were analysed using the Annexin V-PI method. Since NF-kB and TNF-α play important roles in the anti-proliferation and apoptosis pathways, the levels of NF-kB and TNF-α mRNA expression were measured. As a result, bortezomib significantly increased cell apoptosis in cells co-cultured with M0 macrophages. IL-1β cytokine levels also increased, and NF-kB mRNA expression levels decreased. Understanding the mechanisms that modulate the tumour microenvironment may facilitate the development of novel anticancer therapies. The utilisation of TAMs may improve the successful treatment of lung cancer and warrants further study.

 We investigated the fundamental function of the lung cancer tumour microenvironment. Proteasome inhibition has emerged as a clinically successful anti-cancer therapeutic strategy, with the antineoplastic medication bortezomib showing high efficacy against multiple cancers. Tumour-associated macrophages TAMs, which migrate to tumour stroma, are known to promote cell proliferation, apoptosis, and metastasis within the lung cancer microenvironment. However, the specific interaction of macrophages, lung cancer cells, and bortezomib are still unclear. Most in vitro cell cultures are traditionally grown in a two-dimensional 2D culture system, although 3D cultures have demonstrated greater success in terms of drug response, gene expression and viability. Therefore, to elucidate the role of macrophages, we aimed to establish a co-culture model in both 2D and 3D cultures using A549 human lung cancer cells and THP-1 derived macrophages. Apoptotic effects were analysed using the Annexin V-PI method. Since NF-kB and TNF-α play important roles in the anti-proliferation and apoptosis pathways, the levels of NF-kB and TNF-α mRNA expression were measured. As a result, bortezomib significantly increased cell apoptosis in cells co-cultured with M0 macrophages. IL-1β cytokine levels also increased, and NF-kB mRNA expression levels decreased. Understanding the mechanisms that modulate the tumour microenvironment may facilitate the development of novel anticancer therapies. The utilisation of TAMs may improve the successful treatment of lung cancer and warrants further study.

 We investigated the fundamental function of the lung cancer tumour microenvironment. Proteasome inhibition has emerged as a clinically successful anti-cancer therapeutic strategy, with the antineoplastic medication bortezomib showing high efficacy against multiple cancers. Tumour-associated macrophages TAMs, which migrate to tumour stroma, are known to promote cell proliferation, apoptosis, and metastasis within the lung cancer microenvironment. However, the specific interaction of macrophages, lung cancer cells, and bortezomib are still unclear. Most in vitro cell cultures are traditionally grown in a two-dimensional 2D culture system, although 3D cultures have demonstrated greater success in terms of drug response, gene expression and viability. Therefore, to elucidate the role of macrophages, we aimed to establish a co-culture model in both 2D and 3D cultures using A549 human lung cancer cells and THP-1 derived macrophages. Apoptotic effects were analysed using the Annexin V-PI method. Since NF-kB and TNF-α play important roles in the anti-proliferation and apoptosis pathways, the levels of NF-kB and TNF-α mRNA expression were measured. As a result, bortezomib significantly increased cell apoptosis in cells co-cultured with M0 macrophages. IL-1β cytokine levels also increased, and NF-kB mRNA expression levels decreased. Understanding the mechanisms that modulate the tumour microenvironment may facilitate the development of novel anticancer therapies. The utilisation of TAMs may improve the successful treatment of lung cancer and warrants further study.

 We investigated the fundamental function of the lung cancer tumour microenvironment. Proteasome inhibition has emerged as a clinically successful anti-cancer therapeutic strategy, with the antineoplastic medication bortezomib showing high efficacy against multiple cancers. Tumour-associated macrophages TAMs, which migrate to tumour stroma, are known to promote cell proliferation, apoptosis, and metastasis within the lung cancer microenvironment. However, the specific interaction of macrophages, lung cancer cells, and bortezomib are still unclear. Most in vitro cell cultures are traditionally grown in a two-dimensional 2D culture system, although 3D cultures have demonstrated greater success in terms of drug response, gene expression and viability. Therefore, to elucidate the role of macrophages, we aimed to establish a co-culture model in both 2D and 3D cultures using A549 human lung cancer cells and THP-1 derived macrophages. Apoptotic effects were analysed using the Annexin V-PI method. Since NF-kB and TNF-α play important roles in the anti-proliferation and apoptosis pathways, the levels of NF-kB and TNF-α mRNA expression were measured. As a result, bortezomib significantly increased cell apoptosis in cells co-cultured with M0 macrophages. IL-1β cytokine levels also increased, and NF-kB mRNA expression levels decreased. Understanding the mechanisms that modulate the tumour microenvironment may facilitate the development of novel anticancer therapies. The utilisation of TAMs may improve the successful treatment of lung cancer and warrants further study.

Makale detayları

Comparison of the apoptotic effects of bortezomib using 2D and 3D co-culture models of THP-1 derived macrophage and A549 lung cancer

Yazarlar:

Miriş Dikmen | Zerrin Cantürk

Yayıncı:

Marmara University

Ana Başlıklar:

Basic Pharmacology | Medical Pharmacology

Dergi:

Journal of Research in Pharmacy Vol.25 Issue 4, pp.490-499

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001348088

pISSN:

2630-6344

A549

macrophage

THP-1

bortezomib

3D culture.

Sayı

Makale detayları

Comparison of the apoptotic effects of bortezomib using 2D and 3D co-culture models of THP-1 derived macrophage and A549 lung cancer

Yazarlar: Miriş Dikmen | Zerrin Cantürk

Yayıncı: Marmara University

Ana Başlıklar: Basic Pharmacology | Medical Pharmacology

Dergi: Journal of Research in Pharmacy Vol.25 Issue 4, pp.490-499

Belge Tipi: Makale

Yayın Tarihi: 6/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001348088

pISSN: 2630-6344

A549

macrophage

THP-1

bortezomib

3D culture.

Sayı

Yazarlar:

Miriş Dikmen | Zerrin Cantürk

Yayıncı:

Marmara University

Ana Başlıklar:

Basic Pharmacology | Medical Pharmacology

Dergi:

Journal of Research in Pharmacy Vol.25 Issue 4, pp.490-499

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001348088

pISSN:

2630-6344