摘要目的 研究氯化锂对前列腺癌生长的影响并探讨其作用机制.方法 选用人前列腺癌PC-3细胞株,采用体外培养和裸鼠背部皮下移植观察氯化锂对细胞生长的影响,应用四甲基偶氮唑盐(MTT)法、细胞BrdU掺入实验和Western blot方法探讨细胞增殖活性和DNA复制相关蛋白的变化.结果 细胞培养第3天,经10 mmol/L氯化锂处理的前列腺癌PC-3细胞数为1.9×105,与PBS对照组的4.8×105比较差异有统计学意义(P＜0.05).氯化锂及对照组氯化钠、氯化钾处理组的细胞增殖抑制率分别为50％、95％及98％,差异有统计学意义(P＜0.05).在氯化锂浓度为10、30 mmol/L时,BrdU掺入吸光度(A)值分别为1.5、1.3,与PBS对照组为4相比差异有统计学意义(P＜0.05).在氯化锂作用下DNA复制相关蛋白cdc 6、cdc 25C、cyclin A和cyclin E蛋白水平下调、CDK抑制剂p21C1P1蛋白水平上调.动物实验结果示腹腔注射氯化锂组移植瘤的平均体积为50 mm3,平均体质量为296 mg,均明显小于PBS对照组的180mm3和957 mg,差异有统计学意义(P＜0.05).结论 体内外实验氯化锂均可抑制前列腺癌PC-3细胞株生长,其机制可能与阻滞细胞DNA合成有关.

abstractsObjective To assess the effects of LiCl on prostate cancer growth and to explore the underlying mechanisms,Methods Effects of LiCl on cell growth in vitro and in vivo were determined by cell counting and xenografts of prostate cancer cells,Alterations in cell proliferation and the expression of DNA replication-related protein were determined by MTT assay,BrdU incorporation and Western blot.Results Compared to PBS control group,the number of prostate cancer cells(PC-3) were lower treated with 10 mmol/L LiCl,the number was 1.9 × 105,4.8 × 105 and the difference was significant(P ＜ 0.05).The inhibition rate of cellular proliferation were 50％,95％ and 98％,respectively,in LiCl group,NaCl and KCl control group,the difference was significant(P ＜ 0.05).The A-Value of BrdU incorporation was 1.5,1.3 treated with 10 mmol/L,30 mmol/L LiCl,while the A-value of BrdU incorporation was 4 in PBS control group,the difference was significant(P ＜ 0.05).On the protein level,LiCl downregulates expression of cdc 6,cyclins A and cyclins E,and cdc 25C,and upregulates expression of the CDK inhibitor p21CIP1.The mean volume and weight of xenograft tumor were 50 mm3 and 296 mg after LiCl intraperitoneal injection,But PBS control group were 180 mm3 and 957 mg,the difference was significant(P ＜0.05).Conclusion LiCl disrupts DNA replication and suppresses tumor growth of prostate cancer cells in vitro and in vivo.