Restoration of CBX7 expression increases the susceptibility of human lung carcinoma cells to irinotecan treatment
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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.
KeywordsCBX7 Lung Chemotherapy Irinotecan Etoposide Drug resistance
This work was supported by the following grants: PON01-02782 (Nuove strategie nanotecnologiche per la messa a punto di farmaci e presidi diagnostici diretti verso cellule cancerose circolanti), AIRC (IG 11477), POR Campania FSE 2007–2013 (CREMe), PNR-CNR Aging Program 2012–2014, and CNR Flagship Projects (Epigenomics-EPIGEN, Nanomax-DESIRED). We thank Dr. Francesca Borrelli and Dr. Simona Pace, Faculty of Pharmacy, University of Naples “Federico II” (Naples, Italy) for advice on the statistical analysis.
Conflict of interest
No conflict of interest exists.
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