论文部分内容阅读
目的:p~(53)基因被认为是引起细胞凋亡的重要基因之一,并在大肠癌患者中突变率高。突变的患者术后复发率高,预后差,原因之一可能为p~(53)基因突变的肿瘤细胞对化疗药物不敏感。本文通过研究p~(53)基因与目前大肠癌常用化疗药物5-氟尿嘧啶(5-FU)及羟基喜树碱(HCPT)对肿瘤细胞凋亡的影响,旨在进一步探讨p~(53)基因与大肠癌化疗药敏的关系,材料与方法:1997年1月至7月,取我院外科行手术切除的大肠癌标本39例,用PCR-SSCP法对p~(53)基因第5~8外显子进行检测,同时制备肿瘤单细胞悬液,加入5-FU(10μg/ml),5-FU(10μg/ml)+甲酰四氢叶酸钙(FA 5μg/ml),HCPT(0．1μg/ml)及HCPT(0.1μg/ml)+丹参(6μl),用TdT法(DNA断端标记法)分析上述药物对大肠肿瘤细胞凋亡的影响。结果:大肠癌p~(53)基因突变率为43.6%(17/39),药物作用15h后行TdT法检测发现,5-FU的凋亡率为(Z2.15±7.84)%,5-FU+FA为(25.17±8.83)%,HCPT为(22.59±10.47)%,而HCPT+丹参则为(31.85±14.78)%。当按p~(53)基因突变与否分成p~(53)基因突变组及未突变组后发现,p~(53)基因突变组的细胞凋亡率均小于未突变组(5-FU为16.4%vs 26.6%,5-FU+FA为18.5%vs 30.4%,HCPT为17.3%vs 26.7%,HCPT+丹参为24.2%vs37.8%P<0.01)结论:5-FU与HCPT均通过透导大肠肿瘤细胞凋亡来?
OBJECTIVE: The p53 gene is considered to be one of the important genes that cause apoptosis and has a high mutation rate in patients with colorectal cancer. Patients with mutations have a high postoperative recurrence rate and poor prognosis. One of the reasons may be that tumor cells with p53 mutation are insensitive to chemotherapy drugs. This study was designed to further investigate the effect of p53 on the apoptosis of tumor cells using 5-fluorouracil (5-FU) and hydroxycamptothecin (HCPT), two commonly used chemotherapy agents for colorectal cancer, to further explore the p53 gene. Relationships with chemotherapeutic sensitivity of colorectal cancer,Materials and methods: From January to July 1997, 39 patients with colorectal cancer underwent surgical resection in our hospital were treated with PCR-SSCP method. Exon 8 was tested and a single cell suspension was prepared. 5-FU (10 μg/ml), 5-FU (10 μg/ml) + calcium leucovorin (FA 5 μg/ml), and HCPT (0) were added. (1μg/ml), HCPT (0.1μg/ml) + Salvia miltiorrhiza (6μl), TdT method (DNA fragmentation method) was used to analyze the effect of the above drugs on apoptosis of colorectal tumor cells. Results: The mutation rate of p53 gene in colorectal cancer was 43.6% (17/39). TdT assay showed that the apoptosis rate of 5-FU was (Z2.15±7.84)%. FU+FA was (25.17±8.83)%, HCPT was (22.59±10.47)%, while HCPT+Danshinone was (31.85±14.78)%. When the p53 mutation was divided into p53 mutation group and non-mutation group, the apoptotic rate of the p53 mutation group was lower than that of the non-mutation group (5-FU 16.4% vs 26.6%, 5-FU + FA was 18.5% vs 30.4%, HCPT was 17.3% vs 26.7%, HCPT + Salvia was 24.2% vs 37.8% P<0.01) Conclusion: Both 5-FU and HCPT were transduced Colon cancer cell apoptosis comes from?