摘要
目的:建立5-氟尿嘧啶(5-FU)诱导的胃癌多药耐药细胞株BGC823/5-FU,探讨凋亡相关蛋白Survivin、Bcl-2、Bax及caspase-3与其耐药性产生的关系。方法:采用反复短期暴露并逐渐增加5-FU浓度的方法建立胃癌耐药细胞株BGC823/5-FU,MTT法检测此耐药细胞株对5-FU的耐药倍数及其对临床常用化疗药物阿霉素、丝裂霉素和顺铂的交叉耐药性,流式细胞术检测细胞P-糖蛋白的表达和柔红霉素积累量;Western blotting法检测耐药胃癌细胞株BGC823/5-FU与其亲代药物敏感胃癌细胞株BGC823凋亡相关蛋白Survivin、Bcl-2、Bax及caspase-3的表达。结果:成功诱导出胃癌多药耐药细胞株BGC823/5-FU,较其亲代细胞BGC823对5-FU、阿霉素、丝裂霉素和顺铂的耐药性分别提高10.82、2.50、22.23和2.00倍。其P-糖蛋白表达较BGC823细胞增高(P<0.01),柔红霉素积累量较BGC823细胞减低(P<0.01)。与亲代药物敏感BGC823细胞相比,耐药细胞株BGC823/5-FU细胞Survivin表达上升(P<0.05),Bcl-2表达升高(P<0.05),Bax表达下降(P<0.05),caspase-3表达减低(P<0.05)。结论:胃癌细胞株BGC823在5-FU的诱导下可形成多药耐药细胞株BGC823/5-FU,P-糖蛋白、凋亡相关蛋白Survivin、Bcl-2、Bax及caspase-3可能参与其耐药性的形成。
AIM ： To establish the gastric cancerous muhidrug resistance cell stain BGC823/5 - FU and investigate the relationship between the resistance and the expression of apoptosis related protein Survivin, Bcl - 2, Bax and caspase -3. METHODS： Human gastric cancer cell line BGC823 was induced into MDR cell line by intermittent administration of high dose of 5 - FU. MTT assay was used to detect the sensitivity of these MDR cells to some chemotherapeutic agents. Flow cytometry was used to detect the expression of P - glucoprotein and the accumulative value of intracellular daunorubicin （DNR） in these MDR cells. Western blotting was used to detect the expression of Survivin, Bcl -2, Bax and caspase -3. RESULTS： The resistance cell stain BGC823/5 -FU was established, which possessed the ability of 10. 82 fold resistance to 5 - FU and cross - resistance to adriamycin, mitomycin C and cisplatin. The expression of P - glucoprotein was higher in BGC823/5 - FU cells than that in BGC823 cells, while the accumulative value of intracellular DNR was decreased in BGC823/5 - FU cells. Compared with its parent cells, expressions of Bax and caspase - 3 in BGC823/5 - FU cells were significantly down - regulated, surviving and Bcl - 2 were upregulated in BGC823/5 - FU cells. CONCLUSION ： Gastric cancer cell line BGC823 has been induced into MDR cell line BGC823/5 - FU. P - glucoprotein, Survivin, Bcl - 2/Bax ratio and caspase - 3 may play an important role in MDR of BGC823/5 - FU cells.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2008年第11期2167-2170,共4页
Chinese Journal of Pathophysiology
基金
山东省科技攻关项目课题资助(No.2005GG3202087
No.2004GG2202107)
山东省自然科学基金资助项目(No.Y2004C03)
山东省优秀中青年科学家奖励基金资助项目(No.2004BS02007)
关键词
胃肿瘤
氟尿嘧啶
抗药性
多药
细胞凋亡
Stomach neoplasms
Fluorouracil
Drug resistance, multiple
Apoptosis
