c-myc反义寡核苷酸对卵巢癌细胞COC1/DDP顺铂耐药的逆转作用  

c-myc antisense oligodeoxynucleotides in reversion of cisplatin resistance in ovarian cancer cell line COC1/DDP

作　　者：孙迎春[1] 张晓慧[1] 张爱荣[1] 陈官萍[1] 付建武[1] 

机构地区：[1]山东大学第二附属医院妇产科,济南250033

出　　处：《中国肿瘤生物治疗杂志》2007年第3期269-274,共6页Chinese Journal of Cancer Biotherapy

基　　金：山东大学特色专业基金(No39740736)~~

摘　　要：目的:探讨c-myc反义寡核苷酸(antisense oligodeoxynucleotide,ASODN)逆转人卵巢癌细胞顺铂(cisplatin,又称DDP)耐药的可行性。方法:以卵巢癌DDP耐药细胞株COC1/DDP为研究对象,实验组以脂质体为载体分别将c-myc ASODN、c-myc正义寡核苷酸(sense oligodeoxynucleotide,SODN)转染到COC1/DDP细胞内,阴性对照组细胞以同体积的培养液转染。采用计数法检测转染细胞增殖变化,MTT法检测DDP对细胞增殖的抑制率,RT-PCR、免疫组织化学技术分别检测转染细胞及c-myc ASODN治疗后裸鼠移植瘤c-myc mRNA及蛋白的表达,研究c-myc ASODN逆转癌细胞耐药及降低肿瘤恶性表型和成瘤能力的作用。结果:实验组转染ASODN后COC1/DDP细胞增殖被抑制;对DDP的敏感性提高,细胞生长抑制率增高,与SODN组及阴性对照组比较,差异均有统计学意义(P<0.05)。ASODN转染后COC1/DDP细胞的c-myc mRNA和蛋白表达均明显降低,与相同浓度SODN转染组、阴性对照组的COC1/DDP细胞比较,差异均有统计学意义(P<0.05)。裸鼠腹水瘤模型中ASODN+DDP治疗组与单纯DDP治疗组及SODN+DDP治疗组相比较,腹水少、腹腔内瘤块少且体积小、移植瘤中c-myc mRNA和蛋白的表达均明显降低。结论:体外、体内实验中c-myc ASODN均能有效地逆转卵巢癌细胞DDP耐药性,c-myc反义寡核苷酸可望成为一种有效的卵巢癌治疗方法。Objective： To evaluate the feasibility of c-myc antisense oligodeoxynucleotides （ASODN） in reversing cisplatin （DDP） resistance in ovarian cancer cell line COC1/DDP. Methods： COC1/DDP cells were transfected with c-myc ASODN, c-myc sense oligodeoxynucleotides（SODN） , and same volume of culture medium（ negative control） separately by lipofectamine. Cell proliferation was determined by cells counting for 6 days. Then cells were treated with cisplatin and the inhibitory rates of cells were determined by MTT. RT-PCR and immunohistochemistry technique were used to determine the c-myc mRNA and protein in vitro and in vivo. The effectiveness of c-myc ASODN in reversing drug resistance and reducine malignancy/tumorigenesis of COC1/DDP cells was analyzed. Results： Compared with cells in c-myc SODN and negative control groups, those in c-myc ASODN transfected group became sensitive to DDP and their proliferation was significantly inhibited （both P 〈0.05 ）. Expression c-myc mRNA and protein in COC1/DDP cells was significantly decreased in c-myc ASODN group in comparison with that in the other 2 groups （ both P 〈 0. 05 ）. Nude mice intraperitoneally transplanted with ovarian cancer ascites had less ascites, less and small tumors, and decreased expression of c-myc mRAN and protein after they were treated with ASODN ＋ DDP than they were treated with DDP alone or with SODN ＋ DDP. Condusion： c-myc ASODN can reverse the resistance of ovarian cancer cells to cisplatin in vitro and in vivo and it may be a new treatment method for ovarian cancer.

关 键 词：卵巢癌 C-MYC 反义寡核苷酸 顺铂 耐药性 

分 类 号：R737.31[医药卫生—肿瘤]