• 四川大學(xué)華西醫(yī)院普通外科（成都610041）;;
  • 指導(dǎo)老師： 嚴(yán)律南;

目的  介紹目前mdr1基因?qū)е履[瘤對(duì)化療藥物產(chǎn)生多藥耐藥性的研究進(jìn)展。
方法  采用文獻(xiàn)回顧的方式對(duì)腫瘤研究中采用的各種方法逆轉(zhuǎn)mdr1基因?qū)е履[瘤多藥耐藥性的文獻(xiàn)進(jìn)行綜述。
結(jié)果  mdr1基因及其表達(dá)產(chǎn)物P糖蛋白的過度表達(dá)是導(dǎo)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(gè)方面進(jìn)行有效的逆轉(zhuǎn)腫瘤多藥耐藥性。
結(jié)論  單一阻抑mdr1基因或P糖蛋白的表達(dá)，以逆轉(zhuǎn)腫瘤多藥耐藥性的臨床試驗(yàn)結(jié)果并不滿意，多種方法聯(lián)合應(yīng)用是今后逆轉(zhuǎn)腫瘤對(duì)化療藥物多藥耐藥性的研究熱點(diǎn)。

引用本文： 李波,嚴(yán)律南. 逆轉(zhuǎn)mdr1基因?qū)е履[瘤多藥耐藥性的研究進(jìn)展. 中國普外基礎(chǔ)與臨床雜志, 2004, 11(6): 554-557. doi: 復(fù)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. 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. 2. Shapiro AB, Fox K, Lee P, et al. Functional intracellular Pglycoprotein [J]. Int J Cancer, 1998; 76(6)∶857.
  3. 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. 4. Szabo D, Keyzer H, Kaiser HE, et al. Reversal of multidrug resistance of tumor cells [J]. Anticancer Res, 2000; 20(6B)∶4261.
  5. 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. 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. 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. 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. 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. 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. 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. 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. 13. ElOsta A, Wolffe AP. Analysis of chromatinimmunopurified MeCP2associated fragments [J]. Biochem Biophys Res Commun, 2001; 289(3)∶733.
  14. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.