Oligomycin A promotes radioresistance in HT29 colorectal cancer cells and its mechanisms. / 寡éç´ Aå¢å ç»ç´è çHT29ç»èæ¾å°æ²»çæµæåå
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Zhong Nan Da Xue Xue Bao Yi Xue Ban
; 46(2): 113-120, 2021 Feb 28.
Article
em En, Zh
| MEDLINE
| ID: mdl-33678646
ABSTRACT
OBJECTIVES:
Radiotherapy is one of the main therapies for colorectal cancer, but radioresistance often leads to radiotherapy failure. To improve the radioresistance, we explore the effect of oligomycin A, the H+-ATP synthase inhibitor, on the sensitivity of HT29 colorectal cancer cells to irradiation and its underlying mechanisms.METHODS:
The effects of different concentrations of oligomycin A on the survival rate and glycolysis of HT29 colorectal cancer cells at different time points were investigated via MTT and glycolysis assay. siRNA-PFK1 was synthesized in vitro and transfected into HT29 cells. The effects of oligomycin A on radiosensitivity of HT29 colorectal cancer cells were measured via MTT and colony formation assay. Western blotting was used to detect the effect of oligomycin A on the expression of glycolytic enzyme PFK1. We compared difference between the effects of siRNA-PFK1 group and oligomycin A combined with siRNA-PFK1 group on cell survival and glycolysis. After 4 Gy X-ray irradiation, the effects of cell survival and glycolysis between the siRNA-PFK1 group and the oligomycin A combined with siRNA-PFK1 group were compared.RESULTS:
Compared with the 0 µmol/L oligomycin A group, the cell survival rate of HT29 cells treated with 4 µmol/L oligomycin A was significantly increased (P<0.05), and the glucose uptake, the lactic acid, and the ATP production were also significantly increased (all P<0.01). After X-ray irradiation at different doses (0, 2, 4, 6, and 8 Gy), the colony formation rate and cell survival rate of the 4 µmol/L oligomycin A treated group were significantly higher than those in the 0 µmol/L oligomycin A group (both P<0.01). The sensitization enhancement ratio of oligomycin A on HT29 colorectal cancer cells was 0.4886. The expression of PFK1 in the 4 µmol/L oligomycin A group was significantly higher than that in the 0 µmol/L oligomycin A group (P<0.001). The glycolysis level, colony formation rate, and cell survival rate of the siRNA-PFK1 HT29 cells group were significantly lower than those in the 0 µmol/L oligomycin A group (all P<0.05), while the results in the 4 µmol/L oligomycin A combined with siRNA-PFK1 group were significantly higher than those in the siRNA-PFK1 group (all P<0.001). After 4 Gy X-ray irradiation, the colony formation rate and cell survival rate in the siRNA-PFK1 group were decreased compared with those in the irradiation group (P<0.01 or P<0.001), while the results of the 4 µmol/L oligomycin A combined with siRNA-PFK1 group were significantly higher than those in the siRNA-PFK1 group (both P<0.001).CONCLUSIONS:
Oligomycin A can promote the radioresistance of HT29 colorectal cancer cells, which may be related to up-regulation of the PFK1 expression and increase of cell glycolysis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
Limite:
Humans
Idioma:
En
/
Zh
Revista:
Zhong Nan Da Xue Xue Bao Yi Xue Ban
Assunto da revista:
MEDICINA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China