摘要
目的 比较肿瘤细胞对99Tcm 甲氧基异丁基异腈 (MIBI)和99Tcm tetrofosmin的摄取情况 ,研究细胞的药物摄取量与细胞P 糖蛋白 (Pgp)表达水平的关系。方法 用放射性核素示踪法研究人子宫颈癌细胞Hela、人乳腺癌细胞MCF 7、人乳腺癌细胞Bca6 1和抗阿霉素人乳腺癌细胞MCF 7/Adr对99Tcm MIBI和99Tcm tetrofosmin的摄取动力学。研究奎尼丁作用于肿瘤细胞时对肿瘤细胞药物摄取量的影响。用免疫组织化学染色法对这 4种癌细胞的Pgp表达水平进行研究。结果 免疫组化法检测出Hela、MCF 7、Bca6 1的Pgp表达呈阴性 ,MCF 7/Adr的Pgp表达呈强阳性。Pgp阴性的癌细胞对 2种药物的摄取量较高 ,并且对99Tcm MIBI的摄取量较对99Tcm tetrofosmin高 ,而Pgp强阳性的MCF 7/Adr对 2种药物的摄取量很低。奎尼丁可使MCF 7/Adr对99Tcm MIBI和99Tcm tetrofosmin的摄取量分别提高 3.5和 4.3倍。结论 肿瘤细胞Pgp的表达水平与细胞的药物摄取量呈负相关 ,99Tcm tetrofosmin与99Tcm MIBI一样 ,可作为衡量与Pgp相关的多药耐药性的标度。奎尼丁对MCF 7/Adr的耐药性有一定的抑制作用。
Objective To study the relationship between the cellular uptake of 99 Tc m MIBI and 99 Tc m tetrofosmin and the Pgp expression levels in four carcinoma cell lines, and the effect of quinidine on the uptake. Methods 99 Tc m MIBI and 99 Tc m tetrofosmin were used as radioactive tracers to study the uptake kinetics in the carcinoma cell lines Hela, MCF 7, Bca61 and Mcf 7/Adr, and the effect of quinidine on the uptake of 99 Tc m MIBI and 99 Tc m tetrofosmin. The Pgp expression levels in carcinoma cell lines were estimated by using immunocytochemical method. Results The cellular uptake of both 99 Tc m MIBI and 99 Tc m tetrofosmin was remarkably lower in MCF 7/Adr which gave a strong positive reaction in the Pgp immunocytochemical assay than Hela, MCF 7 and Bca61 did, which gave negative reactions in the immunocytochemical assay. Furthermore, the cellular uptake of 99 Tc m MIBI was higher than that of 99 Tc m tetrofosmin in the three Pgp negative carcinoma cell lines. The uptake of 99 Tc m MIBI and 99 Tc m tetrofosmin exhibited a 3.5 fold and a 4.3 fold increase respectively in the presence of quinidine. Conclusions The cellular uptake of these two univalent cationic fat soluble medicines in carcinoma cell lines is negatively correlated with the Pgp expression levels in the cells. Similar to 99 Tc m MIBI, 99 Tc m tetrofosmin seems also to be a good candidate as a noninvasive marker for the diagnosis of multi drug resistance (MDR) relating to the Pgp levels in tumors. Quinidine can inhibit the drug resistance of MCF 7/Adr in some degree.
出处
《中华核医学杂志》
CAS
CSCD
北大核心
2000年第6期266-268,共3页
Chinese Journal of Nuclear Medicine
基金
国家自然科学基金!资助项目 (2 97310 2 0 0 2 )