Advances in Overcoming Multidrug Resistance of Tumors Caused by mdr1Gene_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Bo , YAN Lnan.

Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

Keywords：

Multidrug resistance gene Multidrug resistance

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【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.

Citation： LI Bo,YAN Lnan.. Advances in Overcoming Multidrug Resistance of Tumors Caused by mdr1Gene. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2004, 11(6): 554-557. doi: Copy

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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Advances in Overcoming Multidrug Resistance of Tumors Caused by mdr1Gene

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