Effects of radioactive 125I-seeds on the growth inhibition and apoptosis induction of human lung adenocarcinoma cells A549 in nude mice / 中华放射医学与防护杂志

ABSTRACT

Objective To investigate the inhibitory effects of radioactive 125I seeds on the growth and apoptosis of human lung adenocarcinoma cells A 549 in nude mice.Methods Human lung adenocarcinoma A549 cells were cultured in vitro and subcutaneously transplanted in BALA/c nude mice.When the tumor size reached(300 ±50)mm3,40 tumor-bearing mice were divided into 4 groups by the random number table method as 0,0.6,0.8 mCi(1 Ci＝3.7×1010Bq)groups and blank control group,with 10 in each group.The 125I seeds of 0,0.6,and 0.8 mCi were implanted into the transplanted tumors in nude mouse,respectively.The blank control group received no treatment.The weight of nude mice was measured regularly every 4 days.The mice were sacrificed on the 32 days after 125I seeds implication.The transplanted tumors were weighed and the weight gain curve for nude mice was plotted.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes of the tumor tissue.Cell apoptosis was detected by TUNEL assay,and the expressions of the P21,Caspase-9,Survivin and Livin proteins were detected by immunohistochemical assay.Results There was no nude mice dead in each group.On the day 28 and 32 after 125I seeds treatment,the body weights of nude mice of 0.6 and 0.8 mCi groups became lighter than those of the blank control group(q＝4.26,9.19,4.11,11.59,P＜0.05),the tumor weights of the 0.6 and 0.8 mCi groups were significantly decreased(q＝5.021,5.692,P＜0.05)with tumor inhibition rates of about 49％and 62％.In the 0.6 and 0.8 mCi groups,a large number of tumor cells degenerated to be necrotic cells.In addition,the apoptotic indexes were(50.00 ±2.58)％and(62.33 ± 4.51)％in the 0.6 and 0.8 mCi groups,respectively,and higher than that of blank control group(27.00 ±4.69)％.The expressions of P21 and Caspase-9 proteins in the 0.6 and 0.8 mCi groups were significantly higher than that in the blank control group(χ2＝11.380,24.310,11.380,20.376,P＜0.05).The expressions of Survivin and Livin proteins in the 0.6 and 0.8 mCi groups was significantly lower than that in the blank control group(χ2＝9.643,23.254,15.429,26.667,P＜0.05).Conclusions Radioactive 125I seeds can inhibit the proliferation of tumor cells and promote the apoptosis of A 549 cells probably by up-regulating the expressions of P21 and Caspase-9 but down-regulating the expressions of Survivin and Livin.