Depletion of insulin-like growth factor 1 receptor increases radiosensitivity in colorectal cancer.
Colorectal cancer (CRC)
IGF1R inhibitor
insulin-like growth factor-1 receptor (IGF1R)
radiosensitivity
Journal
Journal of gastrointestinal oncology
ISSN: 2078-6891
Titre abrégé: J Gastrointest Oncol
Pays: China
ID NLM: 101557751
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
entrez:
18
1
2021
pubmed:
19
1
2021
medline:
19
1
2021
Statut:
ppublish
Résumé
Although radiation therapy for advanced colorectal cancer (CRC) is very effective in some patients, treatment resistance limits its efficacy. Insulin-like growth factor 1 receptor (IGF1R) can affect tumor responsiveness and sensitivity to radiation in several cancer types. Herein, we studied the underlying function of IGF1R in the resistance of advanced CRC to radiation therapy and the possible use of drugs targeting IGF1R to overcome this resistance in patients with CRC. Differences in the expression levels of the IGF1R were assessed in CRC samples from patients who were radiosensitive or radioresistant. Two radio-resistant colorectal cancer cell lines, SW480 and HT29, were selected for Compared with tissues from radiosensitive patients, higher IGF1R expression levels were found in patients with radiation-resistant colorectal cancer, while BMS-754807 had improved radiosensitivity and reversed radiation tolerance in both colorectal cancer cell lines. Pre-treatment with BMS-754807 prior to irradiation inhibited Akt phosphorylation, induced cell cycle arrest, and increased DNA damage. Therefore, the IGF1R contributes to radiation resistance of CRC cells This study supports the notion that the radiosensitivity of radiation-resistant colorectal cancer cells can be enhanced by directly targeting IGF1R expression or activity. Ultimately, the combination of radiotherapy with IGF1R targeted inhibitors could potentially increase its effectiveness in the treatment of advanced colorectal cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Although radiation therapy for advanced colorectal cancer (CRC) is very effective in some patients, treatment resistance limits its efficacy. Insulin-like growth factor 1 receptor (IGF1R) can affect tumor responsiveness and sensitivity to radiation in several cancer types. Herein, we studied the underlying function of IGF1R in the resistance of advanced CRC to radiation therapy and the possible use of drugs targeting IGF1R to overcome this resistance in patients with CRC.
METHODS
METHODS
Differences in the expression levels of the IGF1R were assessed in CRC samples from patients who were radiosensitive or radioresistant. Two radio-resistant colorectal cancer cell lines, SW480 and HT29, were selected for
RESULTS
RESULTS
Compared with tissues from radiosensitive patients, higher IGF1R expression levels were found in patients with radiation-resistant colorectal cancer, while BMS-754807 had improved radiosensitivity and reversed radiation tolerance in both colorectal cancer cell lines. Pre-treatment with BMS-754807 prior to irradiation inhibited Akt phosphorylation, induced cell cycle arrest, and increased DNA damage. Therefore, the IGF1R contributes to radiation resistance of CRC cells
CONCLUSIONS
CONCLUSIONS
This study supports the notion that the radiosensitivity of radiation-resistant colorectal cancer cells can be enhanced by directly targeting IGF1R expression or activity. Ultimately, the combination of radiotherapy with IGF1R targeted inhibitors could potentially increase its effectiveness in the treatment of advanced colorectal cancer.
Identifiants
pubmed: 33456988
doi: 10.21037/jgo-20-210
pii: jgo-11-06-1135
pmc: PMC7807270
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1135-1145Informations de copyright
2020 Journal of Gastrointestinal Oncology. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-20-210). The authors have no conflicts of interest to declare
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