title: Restoration of CBX7 expression increases the susceptibility of human lung carcinoma cells to irinotecan treatment.
abstract: Lung cancer is one of the most common causes of cancer-related death worldwide in men and women, and, despite the recent remarkable scientific advances, drug treatment is still unsatisfactory. Polycomb protein chromobox homolog 7 (CBX7) is involved in several biological processes, including development and cancer progression, indeed the lack of CBX7 protein correlates with a highly malignant phenotype and a poor prognosis. However, its role in lung cancer still remains unknown. Since CBX7 is drastically downregulated in human lung carcinomas, we investigated whether restoration of CBX7 expression could affect growth property of lung cancer cells and modulate their sensitivity to treatment with irinotecan and etoposide, two chemoterapy drugs most commonly used in lung cancer therapy. Here, we demonstrate that restoration of CBX7 in two human lung carcinoma cell lines (A549 and H1299), in which this protein is not detectable, leads to a decreased proliferation (at least in part through a downregulation of phosphorylated ERK and phosphorylated p38) and an increased apoptotic cell death after drug exposure (at least in part through the downregulation of Bcl-2, phosphorylated Akt, and phosphorylated JNK). Taken together, these results suggest that the retention of CBX7 expression may play a role in the modulation of chemosensitivity of lung cancer patients to the treatment with irinotecan and etoposide.
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
authors.forename: Nunzio Antonio
authors.initials: NA
authors.lastname: Cacciola
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Sepe
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Forzati
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Federico
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Pellecchia
authors.affiliation: Department of Public Health, University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Malapelle
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: De Stefano
authors.affiliation: Department of Oncology, AORN "V. Monaldi" Hospital, Via L. Bianchi, Naples, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Rocco
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy. alfusco@unina.it.|National Cancer Institute-INCA, Rua Andrè Cavalcanti 37-Centro, CEP 20231-050, Rio de Janeiro, Brazil. alfusco@unina.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.affiliation: Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy. pallante@ieos.cnr.it.
authors.forename: Pierlorenzo
authors.initials: P
authors.lastname: Pallante
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C503627:CBX7 protein, human; D012333:RNA, Messenger; D005047:Etoposide; D000077146:Irinotecan; D063150:Polycomb Repressive Complex 1; D002166:Camptothecin
keywords: CBX7; Chemotherapy; Drug resistance; Etoposide; Irinotecan; Lung