Efficacy of different sequences of radio- and chemotherapy in experimental models of human melanoma

Chiara Arienti, Wainer Zoli, Sara Pignatta, Silvia Carloni, Giulia Paganelli, Paola Ulivi, Antonino Romeo, Enrico Menghi, Anna Sarnelli, Laura Medri, Rolando Polico, Rosella Silvestrini, Anna Tesei

Research output: Contribution to journalArticlepeer-review

Abstract

Although combination chemotherapy and radiotherapy have become the standard of care in numerous tumors, the mechanisms of interaction are often still unclear. The purpose of this study was to analyze the efficacy of radiation treatment and cisplatin sequences and to investigate their mechanisms of interaction. Three melanoma cell lines were used to evaluate in vitro radiation-induced cytotoxicity before and after cisplatin treatment. Expression levels of a panel of genes were determined by real-time RT-PCR. Cytotoxic effect was evaluated by flow cytometry analysis and Comet assay. We also used normal human dermal fibroblasts (HUDE) to evaluate the cytotoxicity of the two treatments by clonogenic assay. Radiation and cisplatin used singly were not particularly effective in reducing proliferation in melanoma cells. Conversely, radiation treatment followed by cisplatin showed a strong synergistic interaction in all cell lines, with a ratio index ranging from 16 to >100. The synergistic effect was accompanied by apoptosis induction (up to 40%) and an increase in the percentage of comet-shaped nucleoids from 85% to 99%. In parallel, our results also showed that radiation treatment of HUDE fibroblasts followed by cisplatin only induced weak cytotoxicity. Our findings highlight the efficacy of the sequence radiation → cisplatin in reducing cell proliferation and in inducing apoptosis in melanoma cell lines. This sequence also modulated a network of proteins involved in DNA damage repair.

Original languageEnglish
Pages (from-to)1548-1556
Number of pages9
JournalJournal of Cellular Physiology
Volume229
Issue number10
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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