Abstract
OBJECTIVE To evaluate preventive and therapeutic effects of recombinant human keratinocyte growth factor (rhKGF) on oral mucositis (OM) and to anticipate clinical utility of rhKGF in OM. METHODS Effect of rhKGF in vitro on 32D-KGFR cell proliferation was evalu-ated by MTT assay. Radiotherapy-induced OM model was induced by 15. 3 Gy 60Co radiotherapy, and rhKGF 0.75, 1.5 and 3 mg-kg~ and palifermin 1.5 mg·kg-1 was iv given, once daily, for 3 d before radiotherapy as preventive treatment, and added rhKGF 1.5 mg·kg-1 on the 2nd and 4th days after radiotherapy as rhKGF preventive + therapeutic treatment. Chemotherapy-induced OM mice were iv given 5 -fluorouracil 50 mg·kg-1 continuously for 4 d, the treatment schedule was simi-lar with the former, however rhKGF 1. 25, 2. 5 and 5 mg·kg-1 and palifermin 2. 5 mg·kg-1 , re-spectively. Clinical observations, food consumption, body mass loss, mortality, OM incidence and severity were monitored. RESULTS rhKGF 6. 25 - 100μg·L-1 could stimulate proliferation of 32D-KGFR cells. In radiotherapy-induced OM model, normal control, model, rhKGF 0. 75 , 1.5 and 3 mg·kg-1 prevention, prevention + therapy and palifermin prevention groups occurred OM with incidence of 0/12, 12/12, 8/12, 6/12, 5/12, 5/12 and 5/12, respectively, of which the last 4 groups significantly increased appetite compared with model group (P <0. 05) on the 6th day after radiotherapy, and on the 6th and 12th days, the body mass in all treatment groups was significantly higher than that in model group (P <0. 05). In addition, the treatment group could decrease OM symptom scores, delay the onset, and shorten the duration. In chemother apy-induced OM model, each group occurred OM with incidence of 0/16, 16/16, 10/16, 8/16, 5/16, 10/16 and 6/16, re-spectively all treatment groups significantly alleviated food consumption loss caused by chemotherapy on the 3rd and 6th day; Compared with model group, rhKGF and palifermin prevention groups obvi-ously increased gut thickness of bowel mucosa, enlarged size of Goblet cells, and boty crypt and vil-lus, while rhKGF prevention + therapy group showed lower potency than prevention of the rhKGF equal dose. CONCLUSION rhKGF is effective on experimental OM and can be used as a prophy-lactic application for OM caused by radiotherapy or chemotherapy for cancer patients.关键词
角质细胞生长因子,人/放射疗法/化学治疗学/口腔黏膜炎/化学预防/治疗Key words
keratinocyte growth factors, human/ radiotherapy/ chemotherapy/ oral mucositis/ chemoprevention/ therapy分类
医药卫生
