中国普外基础与临床杂志

中国普外基础与临床杂志

逆转mdr1基因导致肿瘤多药耐药性的研究进展

查看全文

目的 介绍目前mdr1基因导致肿瘤对化疗药物产生多药耐药性的研究进展。
方法 采用文献回顾的方式对肿瘤研究中采用的各种方法逆转mdr1基因导致肿瘤多药耐药性的文献进行综述。
结果 mdr1基因及其表达产物P糖蛋白的过度表达是导致肿瘤具有多药耐药性的重要原因,可以从mdr1基因的mRNA和P糖蛋白两个方面进行有效的逆转肿瘤多药耐药性。
结论 单一阻抑mdr1基因或P糖蛋白的表达,以逆转肿瘤多药耐药性的临床试验结果并不满意,多种方法联合应用是今后逆转肿瘤对化疗药物多药耐药性的研究热点。

【Abstract】Objective To review the advances in overcoming multidrug resistance of tumors caused by mdr1 gene.
Methods Different ways of overcoming multidrug resistance of tumors caused by mdr1 gene in the literatures were reviewed.
Results One of the important reasons causing multidrug resistance was due to the overexpression of mdr1 gene and its product Pglycoprotein. There were two ways to overcome multidrug resistance of tumors through mdr1 genes mRNA and its product Pglycoprotein effectively.
Conclusion The clinical test of the unitary way to overcome multidrug resistance of tumors is unsatisfactory, combining different ways to overcome multidrug resistance of tumors will be the hot spot of tumors research in the future.

关键词: 多药耐药基因; 多药耐药性

Key words: Multidrug resistance gene Multidrug resistance

引用本文: 李波,严律南. 逆转mdr1基因导致肿瘤多药耐药性的研究进展. 中国普外基础与临床杂志, 2004, 11(6): 554-557. doi: 复制

登录后 ,请手动点击刷新查看全文内容。 没有账号,
1. Chen CJ, Clark D, Ueda K, et al. Genomic organization of the human multidrug resistance (MDR1) gene and origin of Pglycoproteins [J]. J Biol Chem, 1990; 265(1)∶506
2. Shapiro AB, Fox K, Lee P, et al. Functional intracellular Pglycoprotein [J]. Int J Cancer, 1998; 76(6)∶857
3. Molinari A, Calcabrini A, Meschini S, et al. Detection of Pglycoprotein in the Golgi apparatus of druguntreated human melanoma cells [J]. Int J Cancer, 1998; 75(6)∶885
4. Szabo D, Keyzer H, Kaiser HE, et al. Reversal of multidrug resistance of tumor cells [J]. Anticancer Res, 2000; 20(6B)∶4261
5. Ueda K, Pastan I, Gottesman MM. Isolation and sequence of the promoter region of the human multidrugresistance (Pglycoprotein) gene [J]. J Biol Chem, 1987; 262(36)∶17432
6. Kobayashi H, Takemura Y, Wang FS, et al. Retrovirusmediated transfer of antiMDR1 hammerhead ribozymes into multidrugresistant human leukemia cells: screening for effective target sites [J]. Int J Cancer, 1999; 81(6)∶944
7. Gao Z, Gao Z, Fields JZ, et al. Tumorspecific expression of antimdr1 ribozyme selectively restores chemosensitivity in multidrugresistant colonadenocarcinoma cells [J]. Int J Cancer, 1999; 82(3)∶346
8. Marthinet E, Divita G, Bernaud J, et al. Modulation of the typical multidrug resistance phenotype by targeting the MED1 region of human MDR1 promoter [J]. Gene Ther, 2000; 7(14)∶1224
9. Dassow H, Lassner D, Remke H, et al. Modulation of multidrug resistance in human leukemia cells with mdr1targeted antisense oligonucleotides using variable treatment schedules [J]. Int J Clin Pharmacol Ther, 2000; 38(4)∶209
10. Pan L, Tong Y, Jin Y, et al. Reversing drug resistance in the ovarian carcinoma cell line SKOV3/mdr1 in vitro by antisense oligodeoxynucleotides [J]. Chin Med J (Engl), 2001; 114(9)∶929
11. Chan JY, Chu AC, Fung KP. Inhibition of Pglycoprotein expression and reversal of drug resistance of human hepatoma HepG2 cells by multidrug resistance gene (mdr1) antisense RNA [J]. Life Sci, 2000; 67(17)∶2117
12. Ando T, Nishimura M, Oka Y. Decitabine (5Aza2’deoxycytidine) decreased DNA methylation and expression of MDR1 gene in K562/ADM cells [J]. Leukemia, 2000; 14(11)∶1915
13. ElOsta A, Wolffe AP. Analysis of chromatinimmunopurified MeCP2associated fragments [J]. Biochem Biophys Res Commun, 2001; 289(3)∶733
14. Efferth T, Futscher BW, Osieka R. 5Azacytidine modulates the response of sensitive and multidrugresistant K562 leukemic cells to cytostatic drugs [J]. Blood Cells Mol Dis, 2001; 27(3)∶637
15. Sampath J, Sun D, Kidd VJ, et al. Mutant p53 cooperates with ETS and selectively upregulates human MDR1 not MRP1 [J]. J Biol Chem, 2001; 276(42)∶39359
16. Zhan M, Yu D, Lang A, et al. Wild type p53 sensitizes soft tissue sarcoma cells to doxorubicin by downregulating multidrug resistance1 expression [J]. Cancer, 2001; 92(6)∶1556
17. Spitaler M, Utz I, Hilbe W, et al. PKCindependent modulation of multidrug resistance in cells with mutant (V185) but not wildtype (G185) Pglycoprotein by bryostatin 1 [J]. Biochem Pharmacol, 1998; 56(7)∶861
18. Beck JF, Brugger D, Brischwein K, et al. Anticancer drugmediated induction of multidrug resistanceassociated genes and protein kinase C isozymes in the Tlymphoblastoid cell line CCRFCEM and in blasts from patients with acute lymphoblastic leukemias [J]. Jpn J Cancer Res, 2001; 92(8)∶896
19. Ganeshaguru K, Wickremasinghe RG, Jones DT, et al. Actions of the selective protein kinase C inhibitor PKC412 on Bchronic lymphocytic leukemia cells in vitro [J]. Haematologica, 2002; 87(2)∶167
20. Bartsevich VV, Juliano RL. Regulation of the MDR1 gene by transcriptional repressors selected using peptide combinatorial libraries [J]. Mol Pharmacol, 2000; 58(1)∶1
21. Ratnasinghe D, Daschner PJ, Anver MR, et al. Cyclooxygenase2, Pglycoprotein170 and drug resistance; is chemoprevention against multidrug resistance possible? [J]. Anticancer Res, 2001; 21(3C)∶2141
22. Mi Q, Cui B, Silva GL, et al. Pervilleine A, a novel tropane alkaloid that reverses the multidrugresistance phenotype [J]. Cancer Res, 2001; 61(10)∶4030
23. Wang E, Casciano CN, Clement RP, et al. The farnesyl protein transferase inhibitor SCH66336 is a potent inhibitor of MDR1 product Pglycoprotein [J]. Cancer Res, 2001; 61(20)∶7525
24. Nokihara H, Yano S, Nishioka Y, et al. A new quinoline derivative MS209 reverses multidrug resistance and inhibits multiorgan metastases by Pglycoproteinexpressing human small cell lung cancer cells [J]. Jpn J Cancer Res, 2001; 92(7)∶785
25. Wang F, Jiang X, Yang DC, et al. Doxorubicingalliumtransferrin conjugate overcomes multidrug resistance: evidence for drug accumulation in the nucleus of drug resistant MCF7/ADR cells [J]. Anticancer Res, 2000; 20(2A)∶799
26. Yano S, Hanibuchi M, Nishioka Y, et al. Combined therapy with antiPglycoprotein antibody and macrophage colonystimulating factor gene transduction for multiorgan metastases of multidrugresistant human small cell lung cancer in NK celldepleted SCID mice [J]. Int J Cancer, 1999; 82(1)∶105