Lithium chloride increases sensitivity to photon irradiation treatment in primary mesenchymal colon cancer cells.
Mol Med Rep
; 21(3): 1501-1508, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-32016459
ABSTRACT
Colorectal cancer (CRC) is the third most prevalent type of cancer worldwide. It is also the second most common cause of cancerassociated mortality; it accounted for about 9.2% of all cancer deaths in 2018, most of which were due to resistance to therapy. The main treatment for CRC is surgery, generally associated with chemotherapy, radiation therapy and combination therapy. However, while chemoradiotherapy kills differentiated cancer cells, mesenchymal stemlike cells are resistant to this treatment, and this can give rise to therapyresistant tumors. Our previous study isolated T88 primary colon cancer cells from a patient with sporadic colon cancer. These cells exhibited mesenchymal and epithelial features, high levels of epithelialtomesenchymal transition transcription factors, and stemness markers. In addition, it was revealed that lithium chloride (LiCl), a specific glycogen synthase kinase (GSK)3ß inhibitor, induced both the mesenchymaltoepithelial transition and differentiation, and also reduced cell migration, stemness features and cell plasticity in these primary colon cancer cells. The aim of the present study was to investigate the effect of LiCl treatment on the viability of primary colon cancer cells exposed to 7 Gy delivered by highenergy photon beams, which corresponds to 6 megavolts of energy. To achieve this aim, the viability of irradiated T88 cells was compared with that of irradiated T88 cells pretreated with LiCl. As expected, it was observed that LiCl sensitized primary colon cancer cells to highenergy photon irradiation treatment. Notably, the decrease in cell viability was greater with combined therapy than with irradiation alone. To explore the molecular basis of this response, the effect of LiCl on the expression of Bax, p53 and Survivin, which are proteins involved in the apoptotic mechanism and in death escape, was analyzed. The present study revealed that LiCl upregulated the expression of proapoptotic proteins and downregulated the expression of proteins involved in survival. These effects were enhanced by highenergy photon irradiation, suggesting that LiCl could be used to sensitize colon cancer cells to radiation therapy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Radiossensibilizantes
/
Tolerância a Radiação
/
Fótons
/
Cloreto de Lítio
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Itália