摘要
[目的]探讨丹参对人胃癌多药耐药的逆转作用。[方法]以不同浓度的丹参处理胃癌SGC7901及耐药SGC7901/ADR细胞,MTT法检测丹参对两种细胞的毒性及半数抑制率(IC50),流式细胞仪(FCM)检测两种细胞内阿霉素浓度和细胞周期。胃腺癌耐药患者24例,随机分为二组,术前分别用丹参12 g.d-1与阿霉素10mg.m-2和单用阿霉素10 mg.m-2,术后光镜、电镜观察癌组织变化和高效液相色谱法(HPLC)测定细胞内阿霉素浓度。[结果]丹参浓度在500μg/mL以下无细胞毒性,使SGC7901/ADR细胞对阿霉素的IC50由6.01 mg/L增为3.17 mg/L,耐药性得到部分逆转,逆转倍数为1.89(P<0.01);细胞内阿霉素浓度由1.83增加到2.83,增加1.55倍(P<0.05);使细胞周期阻滞于G1、G2期;体内丹参12 g.d-1与阿霉素合用时癌细胞损伤加重,线粒体肿胀嵴变短,数目减少,严重时内、外膜破裂,内质网扩张和囊泡化,伴有膜旁核蛋白体的脱落;癌细胞坏死增多;细胞内阿霉素浓度由45.76增加到133.07,增加2.90倍。[结论]丹参对SGC7901/ADR细胞和胃腺癌阿霉素多药耐药有逆转作用,逆转机制与丹参能增加耐药细胞内化疗药物浓度有关。
[ Objective] To study the effects of Salvia miltiochiga（SAL） reversing the multidrug resistance of the human gastric carcinoma. [ Methods] The sensitive cell line SGC7901 and the multidrug resistance cell line SGC7901/ADR were treated with SAL in different concentration. MTT method is used to detect the toxicity and 50% cell inhibitory concentration（IC50 ） of SAL to them. The flow cytometry （FCM） was used to detect the influence of SAL on the cell lines in concentration of intracellular adriamyc（ADM） and the cell cycle. 24 gastric carcinoma patients volunteering were divided into 2 groups randomly. The patients of one group were treated with 12g d^-1 SAL and ADM, and another with ADM simply before operation. The changes of carcinoma tissue were observed with light microscopy and electron microscopy and the intracellular ADM concentration were detected with HPLC after operation. [ Results] The uncytotoxicity concentration of SAL to the cell line was under 500 ug/mL in vitro. The multidrug resistance of SGC7901/ADR to adriamycin was reversed by SAL, and the reversal fold was 1.89 （ P 〈 0.01 ）. The concentration of intracellular ADM was increased by 1.55 fold （ P 〈 0.05 ）. The cell cycle was blocked in G1 and G2 stage by SAL. When 12 g · d^-1 SAL was used in vivo combining with ADM, the intracellular ADM concentration was increase,and the injury to the carcinoma cell was serious which showed , mitochondrion swelling, crista shortening and decreasing, even the intima and extima disrupting, endoplasmic reticulum dilating and vesiculating accompanying ribosome besides ER shedding. increasing. [ Conclusions ] SAL can reverse intracelluardrug resistance of SGC7901/ADR and the human gastric carcinoma to ADM. The mechanism is related to ADM. The intracellular therapeutic drug concentration of the tumor cells by SAL.
出处
《大连医科大学学报》
CAS
2007年第2期100-102,109,共4页
Journal of Dalian Medical University
基金
辽宁省教育厅基金资助(20272274)
