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.%目的 探讨放射性125I粒子对人肺腺癌细胞株A549裸鼠移植瘤生长抑制及细胞凋亡机制.方法 体外培养人肺腺癌A549 细胞,构建BALA/c裸鼠皮下移植瘤模型,待移植瘤长到(300 ±50)mm3时,将40只荷瘤小鼠采用随机数表法分成4组,分别为空源粒子组(0 mCi组)、0.6和0.8 mCi(1 Ci＝3.7×1010Bq)组和空白对照组,每组10只.将放射性活度为0、0.6和0.8 mCi的125I粒子分别植入裸鼠移植瘤内,空白对照组不作任何处理.每4 天定期测量裸鼠体重,共观察32 d.粒子植入移植瘤32 d后处死裸鼠,称量移植瘤质量,绘制裸鼠体重增长曲线.切取瘤组织采用苏木素-伊红(HE)染色观察肿瘤组织病理学变化;末端脱氧核苷酸转移酶-生物素 dUTP 切口末端标记法(TUNEL)检测肿瘤细胞凋亡;用免疫组织化学法检测凋亡因子P21、Caspase-9、Survivin、Livin蛋白的表达.结果 各组裸鼠无死亡.在放射性粒子植入的第28和32天,0.6 和0.8 mCi组裸鼠体重明显小于空白对照组,差异有统计学意义(q＝4.26、9.19、4.11、11.59,P＜0.05).0.6和0.8 mCi组瘤体质量均小于空白对照组(q＝5.021、5.692,P＜0.05),抑瘤率依次约为49％和62％,而0 mCi组瘤体重与空白对照组比较,差异无统计学意义(P＞0.05).0.6和0.8 mCi组瘤细胞大量变性坏死,0mCi组与空白对照组的瘤细胞排列紧密,未见明显坏死.0.6 和0.8 mCi组的凋亡指数明显增加,分别为(50.00 ±2.58)％和(62.33 ±4.51)％,与空白对照组(27.00 ±4.69)％比较,差异均有统计学意义(q＝14.957、10.918,P＜0.05).P21和Caspase-9蛋白在0.6和0.8 mCi组的表达比空白对照组明显增加,差异有统计学意义(χ2＝11.380、24.310、11.380、20.376,P＜0.05).Survivin和Livin 蛋白在0.6 和0.8 mCi 组的表达比空白对照组明显减少(χ2＝9.643、23.254、15.429、26.667,P＜0.05).结论 放射性125I粒子可以抑制肿瘤细胞的增殖,并可能通过上调P21和Caspase-9表达、下调Survivin和Livin表达促进A549细胞的凋亡.
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