卵巢癌细胞凋亡与端粒酶活性、p53突变的相关性研究

Association of cellular apoptosis with telomerase activity and mutant p53 protein in ovarian cancer

目的研究卵巢癌组织中细胞凋亡与凋亡调控因子——端粒酶活性、p53突变之间的关系。方法TRAP-ELISA法半定量测定卵巢癌组织的端粒酶活性；流式细胞计量术(flow cytometry，FCM)分析细胞凋亡率(Apo)、S期细胞比率(SPF)、p53突变蛋白阳性率。结果①随着临床分期、病理分级的升高及淋巴结转移，Apo、SPF均显著增加(P<0．01、P<0．01、P<0．05)，直线相关分析显示二者中度相关(r=0．65，P<0．01)。②随着临床分期、病理分级的升高及淋巴结转移，端粒酶阳性率、阳性程度及p53突变蛋白阳性率均显著增加(端粒酶活性比较为：P<0．05，P<0．01，P<0．01；p53突变蛋白阳性率比较为：P<0．01，P<0．05，P<0．05)。③随着端粒酶活性增高，p53突变蛋白阳性率、Apo、SPF均显著增加(P均<0．01)。④p53突变蛋白阳性率与Apo无明显相关性(r=0．27，P>0．05)，与SPF轻度相关(r=0．38，P<0．01)。结论端粒酶和p53突变都可通过调节细胞凋亡与增殖来调控卵巢癌的恶性行为及转移潜能。卵巢癌早期，二者都促使细胞增殖失控导致肿瘤发生；随着肿瘤进展，p53调节凋亡与增殖的作用减弱，而端粒酶的作用渐强。联合检测可从不同的分子生物学角度评价卵巢癌的恶性行为及转移潜能，为临床诊疗及判断预后提供依据。

Objective To investigate relationship between the cellular apoptosis and the expression of apoptosis-associated factors-telomerase activity and p53 mutation in the ovarian cancer tissue and their association with the malignancy and metastasis of the cancer. Methods TRAP-ELISA was used to detrermine the telomerase activity. Flow cytometry (FCM) was used to analyze the expression of mutant p53, apoptosis (Apo) and S phase fraction (SPF). Results ① Apo andSPF levels were increased significantly along with the clinical stage (according to FIGO stage) and pathologic grade (P<0.01). They both were significantly higher in patients with lymph node metastasis than in those without (P<0.05). The Apo was correlated moderately with the SPF(r=0.65,P<0.01). ② The positive rates of telemerase activity and expression of mutant p53 both increased significantly along with the clinical stage and pathologic grade(with the telomerase activity changing from P<0.05 to P<0.01 to P<0.01, and the expression of mutant p53 changing from<0.01 toP0.05 to P<0.05). They both are significantly higher in patients with lymph node metastasis than in those without (P<0.01 and P<0.05 respectively). ③ Apo, SPF and expression of mutant p53 increased significantly along with telomerase activity (P<0.01). ④ The expression of mutant p53 had no correlationship with altered apoptosis(r=0.27,P>0.05), but was correlated with SPF(=0.38,P<0.01). Conclusion Telomerase activity and mutant p53 both can regulate the levels of apoptosis and proliferatuion, and the latter in turn may control and reflect the maliganacy and metastasis of the ovarian cancer. However, the telomease and mutant p53 protein differ slightly in action as the cancer advances. Hence it is advised to assess them together, so as to help establish the diagnosis and prognosis of ovarian cancer.