摘要
目的研究PC-SPESⅡ对雄激素非依赖性前列腺癌(AIPCa)基因表达的影响。方法雄性Balb/c-nu/nu裸小鼠20只,随机分为对照、PC-SPESⅡ组,每组10只,接种AIPCa细胞DU145建立动物模型。接种第2天起给药,8周后取肿瘤组织,应用human androgen signaling and prostate cancer gene array基因芯片,分析PC-SPESⅡ引起的基因表达变化。为验证基因芯片结果,选择应用RT-PCR方法检测IGF-1mRNA变化。结果30个基因表达下调,包括AIPCa凋亡耐受基因EIF4EBP和FOXj、AIPCa转化基因ADM和PCNA,AIPCa细胞表面标记物PSCA和FAS,以及侵袭性相关基因IGF-1、Met-1、B-myb等。11个基因表达上调,包括AIPCa细胞生长抑制基因PMEPA1和SFRP4,雄激素依赖性细胞表面标记物TMPPSS2、KLK3(PSA)、DD3和STEAP等。结论PC-SPESⅡ可能通过抑制AIPCa凋亡耐受机制、改善AIPCa表型,恢复雄激素依赖性、降低转移能力等多种途径发挥抗AIPCa作用。
Objective To study the change of gene express of androgen independent prostate cancer （AIPCa） treated by PC-SPESⅡ . Methods Twenty male Balb/c nu/nu nude mice were randomly divided into two groups and 10 mice each. The AIPCa cell DU145 was enoculated with a hypodermic injection. On the day after the injection,mice were fed with the drug every day for 8 weeks. The changes of gene of the DU145 tumor after treated with PC-SPESⅡ were measured using human androgen signaling and prostate cancer gene array and compared with the control. IGF-lmRNA analysis was performed by RT-PCR to test the results of gene array. Results Thirty genes down-regulated significantly, including apoptosis resistance gene EIF4EBP and FOXj, switching from ADPCa to AIPCa related gene ADM and PCNA, AIPCa cell surface markers PSCA and FAS, and genes associated with invasive prostate cancer such as IGF-1, Met-1 ,B-myb and so forth. Eleven genes up-regulated, including gene PMEPA1 and SFRP4 which associated with inhibition of AIPCa cell growth, membrane or surface antigen of androgen independent prostate cancer （ADPCa） cells such as TMPPSS2, KLK3 （PSA）, DD3, STEAP and so forth. Conclusions The possible molecular mechanism of PC-SPESⅡ on AIP Ca is speculated to suppress gene related to apoptosis resistance, restore the androgen dependent phenotype of cell,and decreased the ability of invasive and metastasis of AIPCa.
出处
《复旦学报（医学版）》
CAS
CSCD
北大核心
2008年第1期102-106,共5页
Fudan University Journal of Medical Sciences
