Growth hormone protects colorectal cancer cells from radiation by improving the ability of DNA damage repair.
Mol Med Rep
; 10(1): 486-90, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24788673
ABSTRACT
The present study aimed to examine the effects of recombinant human growth hormone (rhGH) on the sensitivity of a colorectal cancer cell line to radiotherapy, and to investigate its association with DNA damage and repair. Flow cytometry and immunofluorescence were employed to detect growth hormone receptor (GHR) expression in nine human colorectal cancer cell lines. A colony forming assay was performed to measure the colorectal cancer cell proliferation postradiotherapy, as an indicator of radiotherapy sensitivity. The comet assay results were interpreted as an indicator of radiotherapyinduced DNA damage, and growth arrest and DNA damage 45 (GADD45) and apurinic/apyrimidinic endonuclease (APEN) protein expression were quantified with western blot analysis from the same cell lines. The results demonstrated that the colonyforming efficiency (CFE) was significantly increased in HCT8 cells subject to radiotherapy and rhGH pretreatment compared with the cells treated with radiotherapy alone, in a dosedependent manner (0100 mg/l). This effect was enhanced under high doses of radiation (8 Gy; 52.1±2.9 vs. 21.0±2.7; P<0.001) and was ameliorated with GHR neutralizing antibody exposure. By contrast, rhGH preincubation did not change the colony formation rate in GHR() LOVO cells. rhGH intervention reduced the early HCT8 cell DNA damage (21.53±2.88 vs. 36.56±3.93; P=0.003) as well as the following plateau phase, compared with cells treated with radiotherapy alone (5.5±0.42 vs. 9.07±0.84; P=0.012). rhGH upregulated GADD45 and APEN protein expression, which is associated with cellular stress responses and DNA damage repair (P=0.007). The results suggest that rhGH is able to protect colorectal cancer cells from radiation through the interaction with GHR, which is associated with the promotion of DNA damage repair activity.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Hormona del Crecimiento
/
Reparación del ADN
Límite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Año:
2014
Tipo del documento:
Article