摘要
背景与目的:p16基因是原发性肝癌(hepatocellularcarcinoma,HCC)中失活频率很高的抑癌基因之一,应是治疗HCC的理想靶基因。本研究的目的是探讨转入野生型p16cDNA对肝细胞性肝癌细胞生物学行为的影响。方法:用我们构建的p16基因的逆转录病毒表达载体pcLXSN-p16,分别感染p16蛋白表达阴性与表达阳性的肝癌细胞株SNU-449与HepG2.2.15,筛选出稳定的表达株,对转基因后肿瘤细胞的生物学行为进行观察。结果:p16蛋白表达阴性的SNU-449细胞转入野生型p16基因后,细胞生长速度明显减慢,G0-G1期细胞明显多于转基因前,其裸鼠首次接种成瘤率(可在一定程度上反映瘤细胞对组织的侵袭能力)、在裸鼠体内的生长速度以及对裸鼠的致死性均低于未转基因者。而p16蛋白表达阳性的HepG2.2.15细胞转入外源p16cDNA后,其生长状况及细胞周期则未发现有明显改变。就SNU-449与HepG2.2.15细胞株而言,转入p16cDNA均未能诱导细胞凋亡。结论:转入外源野生型p16基因可抑制p16蛋白表达阴性的肝癌细胞的生长并降低其侵袭能力,但对p16蛋白表达阳性的肝癌细胞的生长则无影响。
BACKGROUND &OBJECTIVE:Inactivation of the tumor suppressor g ene p16 INK4a is one of the most common g enetic alte rations in human hepatocellular carcinomas (HCC),making it an ideal targ et g ene for tr eatment of HCC.The objective of this study wa s to investig ate the influence of wil d p16g ene on the biolog ical behavior of HC C.METHODS :HCC cell strains SNU-449(loss of p 16protein expression)and HepG 2.2.15(positive p 16protein expression)were respectively infected by a retr ovirus expression vector of p16g ene(pcLXSN-p16).The stable p16protein expression c ell strains were selected.The biolog ical behaviors of the p16g ene transfected HCC cells were observed.RESULTS :SNU-449with neg ative p16protein expression demonstrated that pcLXSN-p16treat ment sig nificantly inhibited cell g rowth(the amount of cells at G 0 -G 1 phase increased).However,there was no treatment effect when pcLXSN-p16was transfec ted in HepG2.2.15which has positive p16protein expression.Subsequent study in a nude mouse model demonstra ted that the p16g ene transfected SNU-449had a lower succeeding rate of first time establishment of tumors and g rew mor e slowly in the nude mice as compared with non-transfected SNU-449.More over,the nude mice inoculated with transfected SNU-449had a long er sur vival time than those inoculated wit h non-transfected SNU-449.CONCLUSION:The transfer of wild p16g ene can inhibit the proliferation and reduce the invasion ability of HCC cells wi th p16neg ative expression,but can not aff ect the HCC cells with p16positive expression.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2003年第1期46-49,共4页
Chinese Journal of Cancer
