Growth hormone protects colorectal cancer cells from radiation by improving the ability of DNA damage repair.
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 post‑radiotherapy, as an indicator of radiotherapy sensitivity. The comet assay results were interpreted as an indicator of radiotherapy‑induced 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 colony‑forming efficiency (CFE) was significantly increased in HCT‑8 cells subject to radiotherapy and rhGH pretreatment compared with the cells treated with radiotherapy alone, in a dose‑dependent manner (0‑100 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 pre‑incubation did not change the colony formation rate in GHR(‑) LOVO cells. rhGH intervention reduced the early HCT‑8 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.
Department of Gastrointestinal Tumor Surgery, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
Xiao-Yu
XY
Wu
Department of Gastrointestinal Tumor Surgery, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
Che
C
Chen
Department of Gastrointestinal Tumor Surgery, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
Xue-Quan
XQ
Yao
Department of Gastrointestinal Tumor Surgery, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
Qin-Hong
QH
Cao
Department of Gastrointestinal Tumor Surgery, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
Zhe
Z
Xu
Department of Gastrointestinal Tumor Surgery, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
Wei-Su
WS
Li
Department of Gastrointestinal Tumor Surgery, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
Fu-Kun
FK
Liu
Department of General Surgery, Jiangsu Cancer Hospital, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China.
Gang
G
Li
D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D020552:Comet Assay; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D005720:Gamma Rays; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000097642:GADD45 Proteins
D002352:Carrier Proteins; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D013006:Growth Hormone; D047908:Intracellular Signaling Peptides and Proteins; D000097642:GADD45 Proteins; C085108:APEX1 protein, human; C051815:somatotropin-binding protein