Gefitinib对激素非依赖性前列腺癌的治疗及其效应初探

山东大学学报(医学版) ›› 2010, Vol. 48 ›› Issue (1): 52-55.

Gefitinib对激素非依赖性前列腺癌的治疗及其效应初探

陈卫国1，龙慧民2，侯建全1，浦金贤1，严春寅1

1. 苏州大学附属第一医院泌尿外科，江苏苏州 215006； 2. 宁波李惠利医院泌尿外科，浙江宁波 315001

收稿日期:2009-07-07 出版日期:2010-01-16 发布日期:2010-01-16
作者简介:陈卫国(1971- )，男，副主任医师，副教授，医学博士，主要从事前列腺癌的研究。 E-mail:wg.chen@163.com

Inhibitory effect of Gefitinib on hormone independent prostate cancer in vitro and in vivo

CHEN Weiguo1, LONG Huimin2, HOU Jianquan1, PU Jinxian1, YAN Chun yin1

1. Department of Urology, First Affiliated Hospital of Suzhou University, Suzhou215006, Jiangsu, China; 
2. Department of Urology, Ningbo Lihuili Hospital, Ningbo 315001, Zhejiang, China

Received:2009-07-07 Online:2010-01-16 Published:2010-01-16

摘要/Abstract

摘要：

目的探讨受体酪氨酸激酶抑制剂Gefitinib在体内外对激素非依赖前列腺癌（HIPC）的抑制作用及其效应机制。方法不同浓度的Gefitinib处理HIPC细胞株PC-3后24～120h，MTT法检测细胞生长抑制率，Western blot检测细胞表皮生长因子受体（EGFR）、蛋白激酶（Akt）、丝裂原活化蛋白激酶（MAPK）和蛋白激酶C（PKC）蛋白的表达水平。建立PC-3细胞裸鼠移植瘤，观察Gefitinib体内的肿瘤抑制率。结果 Gefitinib抑制PC-3细胞生长呈现时间-浓度依赖性，最佳抑制浓度为5ng/mL，最佳抑制时间为72?h，细胞生长抑制率稳定在50%～60%。与对照组比较，经Gefitinib处理后PC-3细胞中EGFR、Akt蛋白水平分别降低了70.44%和59.01%，而MAPK及PKC蛋白分别仅降低34.83%和33.40%。裸鼠实验结果表明，Gefitinib可显著抑制HIPC肿瘤的生长，抑制率高达53.95%，常规病理HE染色提示大片灶状癌细胞坏死。结论 Gefitinib可在体内外显著抑制HIPC的生长，其机制可能为通过降低癌细胞EGFR和胞内蛋白Akt的表达水平来发挥作用。

关键词: 激素非依赖性前列腺癌；吉非替尼；表皮生长因子受体；胞内效应蛋白

Abstract:

Objective To investigate the inhibitory effect of Gefitinib in the treatment of hormone independent prostate cancer (HIPC) in vitro and in vivo Methods The HIPC cell line PC-3 was treated with Gefitinib indifferent concentrations for 24-120?h, and then the cellinhibition ratio (CIR) was measured with MTT and expression levels of proteins, such as epidermal growth factor receptor (EGFR), protein kinase B (Akt), mitogen aetivatedprotein kinase (MAPK) and protein kinase C (PKC) were determined by Western blot. Results The inhibitoryeffect of Gefitinib on PC-3 cells′ growth showed a time and density- dependence, and the ideal inhibitory concentration and time were 5?ng/mL and 72?h, in which the CIR of PC-3 cells was 50%-60%. Compared with the control group, expression levels of protein EGFR and Akt were significantly decreased by 70.44% and 59.01% in PC-3 cells in the Gefitinib group; expression levels of MAPK and PKC was decreased by 34.83% and 33.40%. In an in vivo experiment, compared with the control group, the growth of HIPC tumors in the Gefitinib group was significantly inhibited by 53.95%.Conclusion Gefitinib could significantly induce inhibitory effects on growth of HIPC in vitro- and in vivo by down-regulation of expressions of EGFR and its intra-cellular effective proteins Akt in PC-3 cells.

Key words: Hormone independence prostate cancer; Gefitinib; Epidermal growth factor receptor; Intracellular effective protein

中图分类号:

R737.25， R730.54

陈卫国1，龙慧民2，侯建全1，浦金贤1，严春寅1. Gefitinib对激素非依赖性前列腺癌的治疗及其效应初探[J]. 山东大学学报(医学版), 2010, 48(1): 52-55.

CHEN Weiguo1, LONG Huimin2, HOU Jianquan1, PU Jinxian1, YAN Chun yin1. Inhibitory effect of Gefitinib on hormone independent prostate cancer in vitro and in vivo[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(1): 52-55.

参考文献

相关文章 12

[1]	高逢彬，司曼飞，刘永青，牛蕾蕾，苑辉卿. 网脊衣酸上调p21CIP1蛋白诱导前列腺癌细胞周期阻滞的作用分析[J]. 山东大学学报(医学版), 2013, 51(12): 34-40.
[2]	郭晓宇1，姜燕2，邢召全3，郭兆新3，房志卿3，刘照旭1,3. DNA甲基化酶抑制剂对前列腺癌中XAF1 mRNA表达的影响[J]. 山东大学学报(医学版), 2012, 50(12): 94-.
[3]	郑桂喜，王传新，张欣，李伟，杜鲁涛，李娟，刘慧. 全人源抗前列腺癌ScFv抗体的筛选及生物学特性研究[J]. 山东大学学报(医学版), 2012, 50(11): 34-38.
[4]	萧畔1,张怀强1,崔亚洲2,赵升田1,马天加1,周春文1. 多西紫杉醇诱导前列腺癌PC3细胞凋亡的蛋白质组学研究[J]. 山东大学学报(医学版), 2012, 50(10): 77-.
[5]	韩博1,3,杨晓庆1,张晶2,刘文君3,刘龙3. SPINK1在前列腺癌中的基础及临床转化研究进展[J]. 山东大学学报(医学版), 2012, 50(8): 40-.
[6]	王海滨，马伟明，萧畔，马天加，张怀强. 热休克蛋白60在多西紫杉醇治疗激素非依赖性前列腺癌过程中的差异表达[J]. 山东大学学报(医学版), 2012, 50(8): 46-50.
[7]	于张健1，张士宝1，刘庆勇1，阮喜云2，杨广笑3，王全颖3. SAC重组腺相关病毒载体的构建及其对前列腺癌CAM移植瘤的抑制作用[J]. 山东大学学报(医学版), 2012, 50(7): 41-.
[8]	陈兆波，刘春艳，倪娜娜，于洋，张鹏举，陈蔚文，姜安丽. miR Let-7a1/f1下调前列腺癌1LNCaP细胞中AMD1蛋白的表达[J]. 山东大学学报(医学版), 2012, 50(1): 29-.
[9]	张士宝刘庆勇阮喜云陈杰张建军李宗武杨广笑王全颖. NT₄-SAC-HA₂-TAT融合基因表达载体的构建及鉴定[J]. 山东大学学报(医学版), 2209, 47(6): 15-19.
[10]	高德轩夏庆华吕家驹张辉. 丙戊酸长期给药对抑制PC3细胞系裸鼠移植瘤生长的影响[J]. 山东大学学报(医学版), 2008, 46(12): 1158-1161.
[11]	. 前列腺癌细胞LNCaP中雄激素依赖性和雄激素非依赖性蛋白差异性表达研究[J]. 山东大学学报(医学版), 2009, 47(9): 62-65.
[12]	张士宝刘庆勇阮喜云陈杰张建军李宗武杨广笑王全颖. NT₄-SAC-HA₂-TAT融合基因表达载体的构建及鉴定[J]. 山东大学学报(医学版), 2009, 47(6): 15-19.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed