华西口腔医学杂志

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银杏酸对口腔鳞癌多药耐药的影响

王辉 周陈晨 冯云 戴丽娜 陈娇 陈思秀 李小玉 刘豫蓉 张平   

  1. 口腔疾病研究国家重点实验室, 四川大学, 四川成都610041
  • 收稿日期:2010-12-25 修回日期:2010-12-25 出版日期:2010-12-20 发布日期:2010-12-20
  • 通讯作者: 张平,Tel:028-85503495
  • 作者简介:王辉(1984—),男,山西人,硕士

The effect of ginkgolic acids on multidrug resistance in oral squamous cell carcinoma

WANG Hui, ZHOU Chen-chen, FENG Yun, DAI Li-na, CHEN Jiao, CHEN Si-xiu, LI Xiao-yu, LIU Yu-rong, ZHANG Ping   

  1. State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
  • Received:2010-12-25 Revised:2010-12-25 Online:2010-12-20 Published:2010-12-20
  • Contact: ZHANG Ping,Tel:028-85503495

摘要:

目的以卡铂(CBP)和平阳霉素(PYM)为诱导物,构建耐药细胞株Tca8113/CBP和Tca8113/PYM,再通过银杏酸(GAs)与化疗药物联用探讨银杏酸对耐药细胞多药耐药(MDR)的影响。方法免疫组织化学检测P-糖蛋白(P-gp)的表达,MTT法确定耐药细胞的耐药指数;不同质量浓度的GAs作用于耐药细胞及亲本细胞,通过MTT法检测对它们的增殖抑制效应,确定GAs的无细胞毒性质量浓度并观察GAs对耐药细胞的逆转作用;GAs与耐药细胞联用诱导细胞一段时间后,再次通过MTT法检测其耐药指数。结果免疫组织化学结果显示,耐药细胞的P-gp阳性表达率明显高于亲本细胞,MTT法确定GAs的无细胞毒性质量浓度为10 μg·mL-1;GAs对Tca8113/CBP和Tca8113/PYM细胞的逆转倍数分别是2.94和2.43,与GAs联用前Tca8113/CBP和Tca8113/PYM细胞的耐药指数分别是3.24和11.9,联用后的耐药指数分别是2.18和4.43。结论本实验成功诱导出了耐药细胞株Tca8113/CBP和Tca8113/PYM,并将银杏酸与化疗药物联用,进一步证实了两者的共用能够增强对Tca8113/CBP和Tca8113/PYM细胞的增殖抑制作用,无细胞毒质量浓度的GAs对Tca8113/CBP和Tca8113/PYM细胞的耐药性有部分逆转作用,且共用一段时间后耐药细胞的MDR水平有所下降。

关键词: 多药耐药, P-糖蛋白, 银杏酸

Abstract:

Objective Carboplatin(CBP)-resistant cell line(Tca8113/CBP) and pingyangmycin(PYM)-resistant cell line(Tca8113/PYM) were established in vitro. Ginkgolic acids’influence over multidrug resistance(MDR) of drug-resistant cells was discussed by ginkgolic acids coupled with chemotherapy drugs. Methods The expression of P-glycoprotein(P-gp) was detected by immunohistochemistry. MTT assay was applied to ascertain the resistance index of drug-resistant cells. The effect of different concentrations of ginkgolic acids on the proliferation of drug-resistant cells and parental cell was measured by MTT assay. Making sure the non-toxic concentration of ginkgolic acids and observing the reversal effect of ginkgolic acids on drug-resistant cells. Resistance index was redetermined by MTT assay after ginkgolic acids coupled with chemotherapy drugs induced the cell lines for some time. Results Immunohistochemistry showed that P-gp positive expression rate of drug-resistant cells was significantly higher than parental cells. The non-toxic concentration of ginkgolic acids which was determined by MTT assay was 10 μg·mL-1. The reversal folds of Tca8113/CBP cell line to CBP and Tca8113/PYM cell line to PYM were 2.94 and 2.43 respectively. Before coupled with ginkgolic acids, the resistance indices of Tca8113/CBP and Tca8113/PYM cell lines were 3.24 and 11.9 respectively. When ginkgolic acids was added with chemotherapy drugs for some time, the resistance indices of Tca8113/CBP and Tca8113/PYM cell lines were 2.18 and 4.43 respectively. Conclusion This experiment successfully induced the drug-resistant cell lines of Tca8113/CBP and Tca8113/PYM. The method of chemotherapy drugs coupled with ginkgolic acids further confirmed the effect on proliferation of Tca8113/CBP and Tca8113/PYM cell lines was reducing. Non-toxic concentration of ginkgolic acids can partially reverse the drug resistance of Tca8113/ CBP and Tca8113/PYM cell lines. Furthermore, MDR level of drug-resistant cells decreased somewhat when they were induced by ginkgolic acids coupled with chemotherapy drugs for some time.

Key words: multidrug resistance, P -glycoprotein, ginkgolic acids