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[多药耐药基因1反义寡脱氧核苷酸逆转卵巢癌细胞系SKOV3多药耐药的研究]

[Study of mdr1 antisense oligodeoxynucleotides on reversal of multidrug resistance in ovarian carcinoma cell line SKOV3].

作者信息

Tong Y, Pan L, Zhou S

机构信息

Department of Obstetrics and Gynecology, General Hospital of Air Force, People's Liberation Army, Beijing 100036, China.

出版信息

Zhonghua Fu Chan Ke Za Zhi. 2000 Nov;35(11):677-9.

Abstract

OBJECTIVE

To investigate the effect of mdr1 antisense oligodeoxynucleotides (ASON) on reversal of multidrug resistance in ovarian carcinoma cells.

METHODS

Drug resistance ovarian carcinoma cells SKOV3/mdr1 transducted with human multidrug resistance gene (mdr1) were served as models. The positive rate and function of the mdr1 gene product P-glycoprotein (P-gp) in SKOV3/mdr1 cells after mdr1-ASON (250 micrograms/ml) treatment were determined by flow cytometry and rhodamine 123 efflux trial. Drug resistance of SKOV3/mdr1 cells was also observed by cell colony culture.

RESULTS

P-gp positive rate of SKOV3/mdr1 cells after mdr1-ASON treatment was decreased from 38.9% to 21.3% (P < 0.01). Intracellular rhodamine retension in SKOV3/mdr1 cells after mdr1-ASON treatment was increased from 32.1% to 50.7% (P < 0.01). Under effect of Taxol 5 ng/ml, the relative percents of drug-resistant colony in mdr1-ASON treated SKOV3/mdr1 cells and in SKOV3/mdr1 cells was 8% and 63%, respectively, (P < 0.01). Under effect of Doxorubicin 100 ng/ml, the relative percents of drug-resistant colony in mdr1-ASON treated SKOV3/mdr1 cells and in SKOV3/mdr1 cells was 34% and 79%, respectively, (P < 0.01).

CONCLUSION

mdr1-ASON can reverse multidrug resistance of ovarian carcinoma cell in a certain extent so as to increase chemotherapeutic sensitivity of ovarian carcinoma cells.

摘要

目的

研究mdr1反义寡脱氧核苷酸(ASON)对卵巢癌细胞多药耐药逆转的作用。

方法

以转导人多药耐药基因(mdr1)的耐药卵巢癌细胞SKOV3/mdr1为模型。采用流式细胞术和罗丹明123外排试验检测mdr1-ASON(250微克/毫升)处理后SKOV3/mdr1细胞中mdr1基因产物P-糖蛋白(P-gp)的阳性率和功能。通过细胞集落培养观察SKOV3/mdr1细胞的耐药性。

结果

mdr1-ASON处理后SKOV3/mdr1细胞的P-gp阳性率从38.9%降至21.3%(P<0.01)。mdr1-ASON处理后SKOV3/mdr1细胞内罗丹明保留率从32.1%升至50.7%(P<0.01)。在5纳克/毫升紫杉醇作用下,mdr1-ASON处理的SKOV3/mdr1细胞和SKOV3/mdr1细胞中耐药集落的相对百分比分别为8%和63%(P<0.01)。在100纳克/毫升阿霉素作用下,mdr1-ASON处理的SKOV3/mdr1细胞和SKOV3/mdr1细胞中耐药集落的相对百分比分别为34%和79%(P<0.01)。

结论

mdr1-ASON可在一定程度上逆转卵巢癌细胞的多药耐药性,从而提高卵巢癌细胞的化疗敏感性。

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