低剂量辐射联合环磷酰胺对肿瘤细胞凋亡、细胞周期及骨髓增殖影响

目的 探讨低剂量辐射联合环磷酰胺对小鼠移植肿瘤细胞的凋亡、细胞周期以及骨髓增殖的影响.方法 昆明种雄性小鼠60只随机分为空白对照组、荷瘤对照组(假照组)、低剂量照射组(LDR组)、CTX化疗组(CTX组)和低剂量照射联合化疗组(LDR CTX组),小鼠左后肢腹股沟皮下接种S180肉瘤细胞(空白组除外),接种后第5、8天LDR组和LDR CTX组小鼠给予γ射线全身照射75 mGy,照射36 h后CTX组和LDR CTX组小鼠采用环磷酰胺(CTX)化疗,测量肿瘤大小变化,并取肿瘤组织采用流式细胞仪分析凋亡、细胞周期,取冲洗骨髓组织分析骨髓增殖情况.结果 与假照组相比,各处理组肿瘤生长缓慢;LDR组肿瘤细胞凋亡增加;CTX组、LDR CTX组G1期细胞比例明显增加,S期细胞比例明显减少,后者较前者为著(t=2.52,P<0.05).与空白对照组相比,假照组、LDR组骨髓细胞浓度未见明显变化,化疗组(CTX组、LDR CTX组)明显减少,后者较前者有明显提高(t= 4.71,P<0.05);CTX组、LDR CTX组的增殖指数(PI)明显增加,LDR CTX组较CTX组进一步升高(t=3.41,P<0.05).结论 低剂量辐射联合环磷酰胺可使机体肿瘤细胞G1期阻滞加剧,对肿瘤增殖细胞杀伤作用增强,明显提高机体抗肿瘤的作用,同时保护机体的骨髓造血机能,具有辅助肿瘤化疗的实际临床意义.

EFFECTS OF LOW DOSE RADIATION COMBINED WITH CYCLOPHOSPHAMIDE ON TUMOR CELL APOPTOSIS, CELL CYCLE AND PROLIFERATION OF BONE MARROW IN TUMOR-BEARING MICE

Objective To study the effect of low-dose radiation (LDR) combined with cyclophosphamide on tumor cell apoptosis, cell cycle and proliferation in bone marrow of tumor-bearing mice. Methods Sixty Kunming strain male mice were randomized into blank group, sham-radiation control, LDR group, CTX chemotherapy group (CTX), and LDR+CTX group. The mice (blank group excluded) were subcutaneously implanted with S180 sarcoma cells in the left hind legs. Five and eight days later, the mice in LDR and LDR+CTX groups were given 75 mGy whole-body γ-ray radiation, 36 hours later, CTX (300 mg/kg) was given to the both groups intraperitoneally. The tumor volume, tumor cell apoptosis, and cell cycle were measure. Proliferation of bone marrow was analyzed by flow cytometry. Results Compared with the sham-radiation group, the tumor grew slowly in all treated groups. The apoptosis of tumor cells increased significantly in LDR group. The tumor cells were arrested in G1 phase in CTX and CTX+LDR groups, but more significantly in the latter (t=2.52,P<0.05). Compared with blank group and sham-radiation group, the concentration of bone marrow cells in CTX and CTX+LDR groups was not much changed, but much lower observed in CTX and CTX+LDR groups, in which, much higher seen in the latter (t=4.71,P<0.05). Proliferation index in CTX+LDR group was higher than that in the LDR group (t=3.41,P<0.05). Conclusion Low-dose radiation combined with cyclophosphamide causes more significant G1-phase arrest than cyclophosphamide alone and enhances anti-tumor effect markedly. LDR significantly protects hematopoetic function of the bone marrow, which is of practical significance in clinical chemotherapy.