p16基因对脑胶质瘤细胞生长及化疗敏感性的影响  

Effects of p16 gene on chemosensitivity of human glioma cell line to teniposide and cisplatin

作　　者：陈一招[1] 徐如祥[1] 张世忠[1] 邹玲[1] 张积仁[2] 张健[2] 

机构地区：[1]第一军医大学珠江医院神经外科,广东广州510282 [2]第一军医大学珠江医院肿瘤科,广东广州510282

出　　处：《中国癌症杂志》2000年第3期198-201,共4页China Oncology

基　　金：国家自然科学基金资助项目 !(批准号 :3970 0 14 3)

摘　　要：目的 :探讨p16基因在脑胶质瘤发生发展过程中的作用及其与脑胶质瘤细胞对鬼臼噻吩苷、顺铂化疗敏感性间的关系。方法 :将外源野生型p16基因导入胶质瘤细胞株U2 5 1,观察p16基因长期稳定转染对胶质瘤细胞的作用 ,并筛选阳性克隆。同时以空载体质粒PCDNA3为对照。Northern杂交检测p16基因表达 ,对转染后细胞生长情况、细胞周期、裸鼠致瘤能力的变化及细胞对鬼臼噻吩苷和顺铂敏感性的变化进行分析。结果 :外源p16基因的高水平表达显著抑制了胶质瘤U2 5 1细胞的生长 ,克隆形成率减少 ,肿瘤细胞发生了G1期阻滞 ,同时 ,细胞对鬼臼噻吩苷和顺铂的敏感性降低 ,其诱导的凋亡细胞数减少。结论 :外源野生型p16基因可抑制胶质瘤细胞恶性增殖 ,同时抑制了鬼臼噻吩苷和顺铂对U2 5 1细胞的诱导凋亡作用进而降低了U2 5 1细胞对鬼臼噻吩苷和顺铂的化疗敏感性。Purpose:To determine the effects on the cell growth,tumorigenicity and chemosensitivity of p16/CDK4I in human glioma. Methods:p16 gene was transfected into U251 cells by lipofectin. Expression of exogenous p16 gene was confirmed by Northern blot. The effects of exogenous p16 gene on the growth and chemosensitivity to teniposide and CDDP were examined. Results:Expression of exogenous p16 gene inhibited the growth of U251 dramatically in vivo and in vitro. G1 arrest of tumor cells was observed. However, wt p16 positive U251 was less sensitive to teniposide and CDDP than control cell lines and the number of apoptotic cells after chemotherapy by teniposide and CDDP was reduced. Conclusions:The expression of exogenous p16 gene could inhibit the growth of glioma. On the other hand, the induction of apoptosis by teniposide and CDDP was inhibited in wt p1 positive U251 and its chemosensitivity to teniposide and CDDP was decreased.

关 键 词：脑胶质瘤 P16基因 鬼臼噻吩苷 顺铂 药物疗法 

分 类 号：R739.41[医药卫生—肿瘤] R73－361[医药卫生—临床医学]