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 language | English |
|---|---|
| Pages (from-to) | 1548-1556 |
| Number of pages | 9 |
| Journal | Journal of Cellular Physiology |
| Volume | 229 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2014 |
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ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology
- Physiology
Cite this
Efficacy of different sequences of radio- and chemotherapy in experimental models of human melanoma. / Arienti, Chiara; Zoli, Wainer; Pignatta, Sara; Carloni, Silvia; Paganelli, Giulia; Ulivi, Paola; Romeo, Antonino; Menghi, Enrico; Sarnelli, Anna; Medri, Laura; Polico, Rolando; Silvestrini, Rosella; Tesei, Anna.
In: Journal of Cellular Physiology, Vol. 229, No. 10, 2014, p. 1548-1556.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Efficacy of different sequences of radio- and chemotherapy in experimental models of human melanoma
AU - Arienti, Chiara
AU - Zoli, Wainer
AU - Pignatta, Sara
AU - Carloni, Silvia
AU - Paganelli, Giulia
AU - Ulivi, Paola
AU - Romeo, Antonino
AU - Menghi, Enrico
AU - Sarnelli, Anna
AU - Medri, Laura
AU - Polico, Rolando
AU - Silvestrini, Rosella
AU - Tesei, Anna
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1002/jcp.24598
DO - 10.1002/jcp.24598
M3 - Article
VL - 229
SP - 1548
EP - 1556
JO - Journal of cellular and comparative physiology
JF - Journal of cellular and comparative physiology
SN - 0021-9541
IS - 10
ER -