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

Giulia Pasello, Loredana Urso, Micol Silic-Benussi, Marco Schiavon, Ilaria Cavallari, Giuseppe Marulli, Nazarena Nannini, Federico Rea, Vincenzo Ciminale, Adolfo Favaretto

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 languageEnglish
Pages (from-to)1008-1017
Number of pages10
JournalJournal of Thoracic Oncology
Volume9
Issue number7
DOIs
Publication statusPublished - 2014

Fingerprint

Pemetrexed
Carboplatin
Apoptosis
Ligands
SCID Mice
Human Activities
Cell Line
Cell Death
TNF-Related Apoptosis-Inducing Ligand Receptors
Aptitude
Combination Drug Therapy
Developed Countries
human TNF protein
Malignant Mesothelioma
Neoplasms
Up-Regulation
Tumor Necrosis Factor-alpha
Drug Therapy
In Vitro Techniques
Incidence

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 journalArticle

Pasello, Giulia ; Urso, Loredana ; Silic-Benussi, Micol ; Schiavon, Marco ; Cavallari, Ilaria ; Marulli, Giuseppe ; Nannini, Nazarena ; Rea, Federico ; Ciminale, Vincenzo ; Favaretto, Adolfo. / 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. In: Journal of Thoracic Oncology. 2014 ; Vol. 9, No. 7. pp. 1008-1017.
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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.",
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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

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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.

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