逆轉mdr1基因導致腫瘤多藥耐藥性的研究進展_《中國普外基礎與臨床雜志》

作者：

李波 , 嚴律南

四川大學華西醫院普通外科（成都610041）;;
指導老師：嚴律南;

關鍵詞：

多藥耐藥基因多藥耐藥性

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目的介紹目前mdr1基因導致腫瘤對化療藥物產生多藥耐藥性的研究進展。
方法采用文獻回顧的方式對腫瘤研究中采用的各種方法逆轉mdr1基因導致腫瘤多藥耐藥性的文獻進行綜述。
結果 mdr1基因及其表達產物P糖蛋白的過度表達是導致腫瘤具有多藥耐藥性的重要原因，可以從mdr1基因的mRNA和P糖蛋白兩個方面進行有效的逆轉腫瘤多藥耐藥性。
結論單一阻抑mdr1基因或P糖蛋白的表達，以逆轉腫瘤多藥耐藥性的臨床試驗結果并不滿意，多種方法聯合應用是今后逆轉腫瘤對化療藥物多藥耐藥性的研究熱點。

引用本文： 李波,嚴律南. 逆轉mdr1基因導致腫瘤多藥耐藥性的研究進展. 中國普外基礎與臨床雜志, 2004, 11(6): 554-557. doi: 復制

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.

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.

《中國普外基礎與臨床雜志》

逆轉mdr1基因導致腫瘤多藥耐藥性的研究進展

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《中國普外基礎與臨床雜志》

逆轉mdr1基因導致腫瘤多藥耐藥性的研究進展

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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