CAJ | 학술논문

目的探讨耐药株人卵巢癌细胞COC1/5-Fu的耐药机制及耐药与细胞凋亡的关系.方法检测COC1/5-Fu细胞株对不同抗肿瘤药物的敏感性,流式细胞仪分析COC1/5-Fu细胞在5-Fu作用的凋亡情况以及对5-Fu的耐受分析,RT-PCR分析COC1/5-Fu细胞株中凋亡相关基因p53、bcl-2、bcl-xl、bax等基因的表达情况.结果 COC1/5-Fu细胞与COC1细胞相比除对5-Fu耐药外,对其它几种常用化疗药均有不同程度的耐药性;COC1细胞未经5-Fu处理的对照组、30μmol/L 5-Fu组及150μmol/L 5-Fu组的凋亡指数与对照组相比,凋亡分别增加了1.2倍和2.1倍,差异有统计学意义(P<0.05),而经同样浓度5-Fu处理的COC1/5-Fu细胞与其对照组相比,细胞凋亡变化不明显(P>0.05);经30μmol/L和150μgmol/L5-Fu处理后,COC1细胞与其对照组相比,呈现明显的G0/G1期增加,S期、G2/M减少.而COC1/5-Fu细胞与其对照组相比细胞周期未见改变;PCR分析发现与COC1细胞相比,COC1/5-Fu细胞耐药株bcl-xl、bcl-xs和bax的表达增高,而p53和cpp32的表达减少,特别是p53基因表达明显减少(P<0.05).结论 wtp53基因的突变与卵巢癌细胞的细胞周期的改变、耐药性的产生相关,是卵巢癌细胞COC1/5-Fu产生多药耐药性的机制之一.
목적 탐토내약주인란소암세포COC1/5-Fu적내약궤제급내약여세포조망적관계.방법 검측COC1/5-Fu세포주대불동항종류약물적민감성,류식세포의분석COC1/5-Fu세포재5-Fu작용적조망정황이급대5-Fu적내수분석,RT-PCR분석COC1/5-Fu세포주중조망상관기인p53、bcl-2、bcl-xl、bax등기인적표체정황.결과 COC1/5-Fu세포여COC1세포상비제대5-Fu내약외,대기타궤충상용화료약균유불동정도적내약성;COC1세포미경5-Fu처리적대조조、30μmol/L 5-Fu조급150μmol/L 5-Fu조적조망지수여대조조상비,조망분별증가료1.2배화2.1배,차이유통계학의의(P<0.05),이경동양농도5-Fu처리적COC1/5-Fu세포여기대조조상비,세포조망변화불명현(P>0.05);경30μmol/L화150μgmol/L5-Fu처리후,COC1세포여기대조조상비,정현명현적G0/G1기증가,S기、G2/M감소.이COC1/5-Fu세포여기대조조상비세포주기미견개변;PCR분석발현여COC1세포상비,COC1/5-Fu세포내약주bcl-xl、bcl-xs화bax적표체증고,이p53화cpp32적표체감소,특별시p53기인표체명현감소(P<0.05).결론 wtp53기인적돌변여란소암세포적세포주기적개변、내약성적산생상관,시란소암세포COC1/5-Fu산생다약내약성적궤제지일.
Objective To explore the mechanism of multi-medicine drug resistance in human ovarian cancer cell line COC1/5-Fu. Methods The apoptosis and the tolerance of COC1/5-Fu cell induced by 5-Fu were analyzed by FACS. The expression of apoptosis related genes, such as p53, bcl-2, bcl-xl and bax, in COCI/5-Fu cell line were analyzed by RT-PCR. Results The COC1/5-Fu cell has some de-gree of drug resistance to 5-Fu and several other commonly used kind of chemotherapy medicine, among of which, drug resistance of 5-Fu reach 107.0 times and Paclitaxel reach 9.0 times compared with COC1. When COC1 was treated with the concentration of 5-Fu (0μmo/L, 30μmo/L or 150 μmol/L), the AI was (6.5±1.0) %, (14.0±4.0) % and (20.0±5.0) %, respectively. The rate of apoptosis increased 1.2 time and 2.1 time, compared with not treated with 5-Fu, which were significantly different (P<0.05). But when COC1/5-Fu was treated with the same concentration of 5-Fu (30 μmo/L or 150 μmoL/L), the AI was (6.7±0.7)%, (7.1±2.2)% and (6.5±2.0)%. When treated with the same concentration of 5-Fu (30 μmo/L or 150 μmol/L) , the proportion of apoptosis was significantly increased, G0/G1 phase was increased, and S and G2/ M phases were reduced in COC1 cells, but the proportion of apoptosis and cell cycle was not changed in COC1/5-Fu cells. The expression of bcl-xl , bcl-xs and bax mRNA were significantly increased and the expression of p53 and cpp32 mRNA were significantly decreased in resistant COC1/5-Fu cells , compared with COC1 cells. Conclusion wtp53 gene mutation is related with cell cycle change of ovary cancer cell and drug resistance, which is one of multi- medicine drug resistance mechanisms of COC1/5-Fu.