DOI QR코드

DOI QR Code

Knockdown of MDR1 Increases the Sensitivity to Adriamycin in Drug Resistant Gastric Cancer Cells

  • Zhu, Chun-Yu (School of Basic Medical Sciences, Xinxiang Medical University) ;
  • Lv, Yan-Ping (Department of Respiratory Medicine, Zhoukou Central Hospital) ;
  • Yan, Deng-Feng (Respiratory Intensive Care Unit (RICU)) ;
  • Gao, Fu-Lian (School of Basic Medical Sciences, Xinxiang Medical University)
  • Published : 2013.11.30

Abstract

Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multiple drug resistance (MDR) to chemotherapy is known as the major cause of treatment failure for gastric cancer. Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp) contributes to drug resistance via ATP-dependent drug efflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1 knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistant gastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drug-sensitivity. Two shRNAs efficiently inhibited mRNA and protein expression of MDR1 in SGC7901-MDR1 cells. MDR1 knockdown obviously decreased the ADR accumulation in cells and increased the sensitivity to ADR treatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells.

Keywords

References

  1. Cole SP, Bhardwaj G, Gerlach JH, et al (1992). Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science, 258, 1650-4. https://doi.org/10.1126/science.1360704
  2. Dong X, Mumper RJ (2010). Nanomedicinal strategies to treat multidrug-resistant tumors: current progress. Nanomedicine (Lond), 5, 597-615. https://doi.org/10.2217/nnm.10.35
  3. Duan Z, Lamendola DE, Duan Y, et al (2005). Description of paclitaxel resistance-associated genes in ovarian and breast cancer cell lines. Cancer Chemother Pharmacol, 55, 277-85. https://doi.org/10.1007/s00280-004-0878-y
  4. Filipits M, Malayeri R, Suchomel RW, et al (1999). Expression of the multidrug resistance protein (MRP1) in breast cancer. Anticancer Res, 19, 5043-9.
  5. Goda K, Fenyvesi F, Bacso Z, et al (2007). Complete inhibition of P-glycoprotein by simultaneous treatment with a distinct class of modulators and the UIC2 monoclonal antibody. J Pharmacol Exp Ther, 320, 81-8.
  6. He Y, Bi Y, Hua Y, et al (2011). Ultrasound microbubble-mediated delivery of the siRNAs targeting MDR1 reduces drug resistance of yolk sac carcinoma L2 cells. J Exp Clin Cancer Res, 30, 104. https://doi.org/10.1186/1756-9966-30-104
  7. Hilgendorf C, Spahn-Langguth H, Rhedin M, et al (2005). Selective downregulation of the MDR1 gene product in Caco-2 cells by stable transfection to prove its relevance in secretory drug transport. Mol Pharm, 2, 64-73. https://doi.org/10.1021/mp049931y
  8. Hua J, Mutch DG, Herzog TJ (2005). Stable suppression of MDR-1 gene using siRNA expression vector to reverse drug resistance in a human uterine sarcoma cell line. Gynecol Oncol, 98, 31-8. https://doi.org/10.1016/j.ygyno.2005.03.042
  9. Huang C, Li Y, Cao P, Xie Z, Qin Z (2011). Synergistic effect of hyperthermia and neferine on reverse multidrug resistance in adriamycin-resistant SGC7901/ADM gastric cancer cells. J Huazhong Univ Sci Technolog Med Sci, 31, 488-96. https://doi.org/10.1007/s11596-011-0478-0
  10. Kroger N, Achterrath W, Hegewisch-Becker S, Mross K, Zander A.R (1999). Current options in treatment of anthracycline-resistant breast cancer. Cancer Treat Rev, 25, 279-91. https://doi.org/10.1053/ctrv.1999.0137
  11. Kruhn A., Wang A., Fruehauf JH, Lage H (2009). Delivery of short hairpin RNAs by transkingdom RNA interference modulates the classical ABCB1-mediated multidrug-resistant phenotype of cancer cells. Cell Cycle, 8, 3349-54. https://doi.org/10.4161/cc.8.20.9845
  12. Leonard GD, Fojo T, Bates SE (2003). The role of ABC transporters in clinical practice. Oncologist, 8, 411-24. https://doi.org/10.1634/theoncologist.8-5-411
  13. Li Y, Yan PW, Huang XE, Li CG (2011). MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. Asian Pac J Cancer Prev, 12, 2405-9.
  14. Liu C, Zhao G, Liu J, et al (2009). Novel biodegradable lipid nano complex for siRNA delivery significantly improving the chemosensitivity of human colon cancer stem cells to paclitaxel. J Control Release, 140, 277-83. https://doi.org/10.1016/j.jconrel.2009.08.013
  15. Liu J, Zhang Y, Xu R, et al (2013). PI3K/Akt-dependent phosphorylation of GSK3beta and activation of RhoA regulate Wnt5a-induced gastric cancer cell migration. Cell Signal, 25, 447-56. https://doi.org/10.1016/j.cellsig.2012.10.012
  16. O’Driscoll L, Clynes M (2006a). Biomarkers and multiple drug resistance in breast cancer. Curr Cancer Drug Targets, 6, 365-84. https://doi.org/10.2174/156800906777723958
  17. O’Driscoll L, Clynes M (2006b). Molecular markers of multiple drug resistance in breast cancer. Chemotherapy, 52, 125-9. https://doi.org/10.1159/000092540
  18. Ozben T (2006). Mechanisms and strategies to overcome multiple drug resistance in cancer. FEBS Lett, 580, 2903-9. https://doi.org/10.1016/j.febslet.2006.02.020
  19. Pan GD, Yang JQ, Yan LN, et al (2009). Reversal of multi-drug resistance by pSUPER-shRNA-mdr1 in vivo and in vitro. World J Gastroenterol, 15, 431-40. https://doi.org/10.3748/wjg.15.431
  20. Song W, Jiang R, Zhao CM (2012). Role of integrin-linked kinase in multi-drug resistance of human gastric carcinoma SGC7901/DDP cells. Asian Pac J Cancer Prev, 13, 5619-25. https://doi.org/10.7314/APJCP.2012.13.11.5619
  21. Stege A, Kruhn A, Lage H (2010). Overcoming multidrug resistance by RNA interference. Methods Mol Biol, 596, 447-65. https://doi.org/10.1007/978-1-60761-416-6_20
  22. Szakacs G, Annereau JP, Lababidi S, et al (2004). Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells. Cancer Cell, 6, 129-37. https://doi.org/10.1016/j.ccr.2004.06.026
  23. Wang J, Li J, Huang Y, et al (2013). Bcl-3 suppresses Tax-induced NF-kappaB activation through p65 nuclear translocation blockage in HTLV-1-infected cells. Int J Oncol, 42, 269-76. https://doi.org/10.3892/ijo.2012.1685
  24. Yamauchi M, Kumazawa H, Satta T, et al (1992). Prediction of doxorubicin resistance in gastrointestinal cancer by P-glycoprotein staining. Eur J Cancer, 28A, 1422-7.
  25. Zhang D, Fan D (2007). Multidrug resistance in gastric cancer: recent research advances and ongoing therapeutic challenges. Expert Rev Anticancer Ther, 7, 1369-78. https://doi.org/10.1586/14737140.7.10.1369
  26. Zhang KG, Qin CY, Wang HQ, Wang JX, Wang QM (2012). The effect of TRAIL on the expression of multidrug resistant genes MDR1, LRP and GST-pi in drug-resistant gastric cancer cell SGC7901/VCR. Hepatogastroenterology, 59, 2672-6.

Cited by

  1. Luteolin-loaded Phytosomes Sensitize Human Breast Carcinoma MDA-MB 231 Cells to Doxorubicin by Suppressing Nrf2 Mediated Signalling vol.15, pp.13, 2014, https://doi.org/10.7314/APJCP.2014.15.13.5311
  2. Establishment and Partial Characterization of an Epirubicin-Resistant Gastric Cancer Cell Line with Upregulated ABCB1 vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6849
  3. Association between ABCB1 Immunohistochemical Expression and Overall Survival in Gastric Cancer Patients vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6935
  4. Pemetrexed is Mildly Active with Good Tolerability in Treating Patients with Gastric Cancer vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7137
  5. EGF Reverses Multi-drug Resistance via the p-ERK Pathway in HepG2/ADM and SMMC7721/ADM Hepatocellular Carcinoma Models vol.15, pp.6, 2014, https://doi.org/10.7314/APJCP.2014.15.6.2619
  6. Silencing of the ABCC4 gene by RNA interference reverses multidrug resistance in human gastric cancer vol.33, pp.3, 2014, https://doi.org/10.3892/or.2014.3702
  7. CIP-36, a novel topoisomerase II-targeting agent, induces the apoptosis of multidrug-resistant cancer cells in vitro vol.35, pp.3, 2014, https://doi.org/10.3892/ijmm.2015.2068
  8. RNAi-based Knockdown of Multidrug Resistance-associated Protein 1 is Sufficient to Reverse Multidrug Resistance of Human Lung Cells vol.15, pp.24, 2014, https://doi.org/10.7314/APJCP.2014.15.24.10597
  9. Inhibitory Effects of Phenolic Alkaloids of Menispermum Dauricum on Gastric Cancer in Vivo vol.15, pp.24, 2015, https://doi.org/10.7314/APJCP.2014.15.24.10825
  10. Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK) vol.26, pp.3, 2015, https://doi.org/10.1091/mbc.E14-10-1443
  11. Hurdles in selection process of nanodelivery systems for multidrug-resistant cancer vol.142, pp.10, 2016, https://doi.org/10.1007/s00432-016-2167-7
  12. Genetic Variation in the ABCB1 Gene May Lead to mRNA Level Chabge: Application to Gastric Cancer Cases vol.16, pp.18, 2016, https://doi.org/10.7314/APJCP.2015.16.18.8467
  13. Influence of Genotype and Haplotype of MDR1 (C3435T, G2677A/T, C1236T) on the Incidence of Breast Cancer - a Case-Control Study in Jordan vol.17, pp.1, 2016, https://doi.org/10.7314/APJCP.2016.17.1.261
  14. The Pattern of Signatures in Gastric Cancer Prognosis vol.19, pp.6, 2018, https://doi.org/10.3390/ijms19061658
  15. Forkhead box O3 promotes colon cancer proliferation and drug resistance by activating MDR1 expression pp.23249269, 2019, https://doi.org/10.1002/mgg3.554
  16. Artemisinin inhibits angiogenesis by regulating p38 MAPK/CREB/TSP-1 signaling pathway in osteosarcoma pp.07302312, 2019, https://doi.org/10.1002/jcb.28424