Abstract
Introduction: Malignant pleural mesothelioma (MPM) is an aggressive, currently incurable tumor with increasing incidence in industrialized countries. Tumor necrosis factor-related, apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which induces cancer cell death through extrinsic apoptotic pathway, while sparing normal cells. The aim of this study was to investigate the antitumor activity of recombinant human Apo2L/TRAIL (dulanermin) in combination with chemotherapy in MPM in vitro and in vivo. Methods: In the present studies, we employed a panel of MPM cell lines to test the antitumor activity of recombinant human Apo2L/TRAIL (T) in combination with carboplatin and pemetrexed (CP) in vitro and SCID mice. Results: Results demonstrated a significant increase of apoptosis in cell lines treated with CPT compared with those receiving CP or T as single agents. This synergistic effect was dependent on the ability of CP to increase the expression of the TRAIL receptors DR4 and DR5 in a p53 manner. The CPT combination was also effective in blocking the growth of MPM cell lines in a SCID mice preclinical model. Conclusions: CPT increases MPM cell death in vitro and in vivo compared with CP. In vitro Results suggest that chemotherapy sensitizes MPM to TRAIL-dependent apoptosis through p53 activation and subsequent upregulation of DRs.
| Original language | English |
|---|---|
| Pages (from-to) | 1008-1017 |
| Number of pages | 10 |
| Journal | Journal of Thoracic Oncology |
| Volume | 9 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- Chemotherapy
- Mesothelioma
- p53
- RhApo2L/TRAIL
ASJC Scopus subject areas
- Oncology
- Pulmonary and Respiratory Medicine
- Medicine(all)
Cite this
Synergistic antitumor activity of recombinant human Apo2L/Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in combination with carboplatin and pemetrexed in malignant pleural mesothelioma. / Pasello, Giulia; Urso, Loredana; Silic-Benussi, Micol; Schiavon, Marco; Cavallari, Ilaria; Marulli, Giuseppe; Nannini, Nazarena; Rea, Federico; Ciminale, Vincenzo; Favaretto, Adolfo.
In: Journal of Thoracic Oncology, Vol. 9, No. 7, 2014, p. 1008-1017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synergistic antitumor activity of recombinant human Apo2L/Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in combination with carboplatin and pemetrexed in malignant pleural mesothelioma
AU - Pasello, Giulia
AU - Urso, Loredana
AU - Silic-Benussi, Micol
AU - Schiavon, Marco
AU - Cavallari, Ilaria
AU - Marulli, Giuseppe
AU - Nannini, Nazarena
AU - Rea, Federico
AU - Ciminale, Vincenzo
AU - Favaretto, Adolfo
PY - 2014
Y1 - 2014
N2 - Introduction: Malignant pleural mesothelioma (MPM) is an aggressive, currently incurable tumor with increasing incidence in industrialized countries. Tumor necrosis factor-related, apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which induces cancer cell death through extrinsic apoptotic pathway, while sparing normal cells. The aim of this study was to investigate the antitumor activity of recombinant human Apo2L/TRAIL (dulanermin) in combination with chemotherapy in MPM in vitro and in vivo. Methods: In the present studies, we employed a panel of MPM cell lines to test the antitumor activity of recombinant human Apo2L/TRAIL (T) in combination with carboplatin and pemetrexed (CP) in vitro and SCID mice. Results: Results demonstrated a significant increase of apoptosis in cell lines treated with CPT compared with those receiving CP or T as single agents. This synergistic effect was dependent on the ability of CP to increase the expression of the TRAIL receptors DR4 and DR5 in a p53 manner. The CPT combination was also effective in blocking the growth of MPM cell lines in a SCID mice preclinical model. Conclusions: CPT increases MPM cell death in vitro and in vivo compared with CP. In vitro Results suggest that chemotherapy sensitizes MPM to TRAIL-dependent apoptosis through p53 activation and subsequent upregulation of DRs.
AB - Introduction: Malignant pleural mesothelioma (MPM) is an aggressive, currently incurable tumor with increasing incidence in industrialized countries. Tumor necrosis factor-related, apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which induces cancer cell death through extrinsic apoptotic pathway, while sparing normal cells. The aim of this study was to investigate the antitumor activity of recombinant human Apo2L/TRAIL (dulanermin) in combination with chemotherapy in MPM in vitro and in vivo. Methods: In the present studies, we employed a panel of MPM cell lines to test the antitumor activity of recombinant human Apo2L/TRAIL (T) in combination with carboplatin and pemetrexed (CP) in vitro and SCID mice. Results: Results demonstrated a significant increase of apoptosis in cell lines treated with CPT compared with those receiving CP or T as single agents. This synergistic effect was dependent on the ability of CP to increase the expression of the TRAIL receptors DR4 and DR5 in a p53 manner. The CPT combination was also effective in blocking the growth of MPM cell lines in a SCID mice preclinical model. Conclusions: CPT increases MPM cell death in vitro and in vivo compared with CP. In vitro Results suggest that chemotherapy sensitizes MPM to TRAIL-dependent apoptosis through p53 activation and subsequent upregulation of DRs.
KW - Chemotherapy
KW - Mesothelioma
KW - p53
KW - RhApo2L/TRAIL
UR - http://www.scopus.com/inward/record.url?scp=84902536234&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84902536234&partnerID=8YFLogxK
U2 - 10.1097/JTO.0000000000000198
DO - 10.1097/JTO.0000000000000198
M3 - Article
VL - 9
SP - 1008
EP - 1017
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 7
ER -