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Current Medical Science

, Volume 38, Issue 6, pp 1018–1024 | Cite as

DJ-1 Alters Epirubicin-induced Apoptosis via Modulating Epirubicinactivated Autophagy in Human Gastric Cancer Cells

  • Xue-kai Pan
  • Fei Su
  • Li-hua Xu
  • Zhang-shuo Yang
  • Dan-wen Wang
  • Li-jie Yang
  • Fan-zheng Kong
  • Wei Xie
  • Mao-hui Feng
Article
  • 5 Downloads

Summary

Epirubicin, which is a conventional chemotherapeutic drug for gastric cancer, has innate and adaptive chemoresistance. Recent studies revealed that epirubicin could induce autophagy as a defensive mechanism in drug resistance of mammary carcinoma. Another study implied that DJ-1 may be a chemoresistance-related gene. But the association between DJ-1 and drug resistance of epirubicin in gastric cancer is still ambiguous. In the present report, we explored whether and how DJ-1 conduced to epirubicin-induced apoptosis in gastric cancer. Epirubicin dose-dependently increased the expression of DJ-1 and induced autophagy. Knockdown of DJ-1 notably enhanced epirubicin-induced cell apoptosis, whereas overexpression of DJ-1 attenuated epirubicin-induced cell apoptosis. Further studies revealed that down-regulation of DJ-1 modulated epirubicinactivated autophagy which augmented epirubicin-induced apoptosis. In conclusion, our results validated that DJ-1 reduced epirubicin-induced apoptosis in gastric cancer cells via modulating epirubicin-activated autophagy.

Key words

epirubicin gastric cancer DJ-1 apoptosis autophagy 

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References

  1. 1.
    Karimi P, Islami F, Anandasabapathy S, et al. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev, 2014,23(5):700–713CrossRefGoogle Scholar
  2. 2.
    An X, Wang F, Shao Q, et al. MET amplification is not rare and predicts unfavorable clinical outcomes in patients with recurrent/metastatic gastric cancer after chemotherapy. Cancer, 2014,120(5):675–682CrossRefGoogle Scholar
  3. 3.
    Tsuburaya A, Mizusawa J, Tanaka Y, et al. Neoadjuvant chemotherapy with S-1 and cisplatin followed by D2 gastrectomy with para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis. Br J Surg, 2014,101(6):653–660CrossRefGoogle Scholar
  4. 4.
    Nakajima T, Fujii M. What make differences in the outcome of adjuvant treatments for resected gastric cancer? World J Gastroenterol, 2014,20(33):11567–11573CrossRefGoogle Scholar
  5. 5.
    Waddell T, Chau I, Cunningham D, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol, 2013,14(6):481–489CrossRefGoogle Scholar
  6. 6.
    Smyth EC, Fassan M, Cunningham D, et al. Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial. J Clin Oncol, 2016,34(23):2721–2727CrossRefGoogle Scholar
  7. 7.
    Nagakubo D, Taira T, Kitaura H, et al. DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras. Biochem Biophys Res Commun, 1997,231(2):509–513CrossRefGoogle Scholar
  8. 8.
    Mémin E, Hoque M, Jain MR, et al. Blocking eIF5A modification in cervical cancer cells alters the expression of cancer-related genes and suppresses cell proliferation. Cancer Res, 2014,74(2):552–562CrossRefGoogle Scholar
  9. 9.
    Ismail IA, Kang HS, Lee HJ, et al. DJ-1 upregulates breast cancer cell invasion by repressing KLF17 expression. Br J Cancer, 2014,110(5):1298–1306CrossRefGoogle Scholar
  10. 10.
    Gao H, Niu Y, Li M, et al. Identification of DJ-1 as a contributor to multidrug resistance in human small-cell lung cancer using proteomic analysis. Int J Exp Pathol, 2017,98(2):67–74CrossRefGoogle Scholar
  11. 11.
    Li Q, Tang Y, Qin J, et al. Subcellular localization of DJ-1 in human HL-60 leukemia cells in response to diallyl disulfide treatment. Mol Med Rep, 2016,14(5):4666–4672CrossRefGoogle Scholar
  12. 12.
    Zeng HZ, Qu YQ, Zhang WJ, et al. Proteomic analysis identified DJ-1 as a cisplatin resistant marker in nonsmall cell lung cancer. Int J Mol Sci, 2011,12(6):3489–3499CrossRefGoogle Scholar
  13. 13.
    Chen Y, Kang M, Lu W, et al. DJ-1, a novel biomarker and a selected target gene for overcoming chemoresistance in pancreatic cancer. J Cancer Res Clin Oncol, 2012,138(9):1463–1474CrossRefGoogle Scholar
  14. 14.
    Lev N, Barhum Y, Pilosof NS, et al. DJ-1 protects against dopamine toxicity: implications for Parkinson's disease and aging. J Gerontol A Biol Sci Med Sci, 2013,68(3):215–225CrossRefGoogle Scholar
  15. 15.
    Saraswathy M, Gong S. Different strategies to overcome multidrug resistance in cancer. Biotechnol Adv, 2013,31(8):1397–1407CrossRefGoogle Scholar
  16. 16.
    Yamamoto Y, Hyodo I, Takigahira M, et al. Effect of combined treatment with the epirubicin-incorporating micelles (NC-6300) and 1, 2-diaminocyclohexane platinum (II)-incorporating micelles (NC-4016) on a human gastric cancer model. Int J Cancer, 2014,135(1):214–223CrossRefGoogle Scholar
  17. 17.
    Chen W, Liu X, Xiao Y, et al. Overcoming multiple drug resistance by spatial-temporal synchronization of epirubicin and pooled siRNAs. Small, 2015,11(15):1775–1781CrossRefGoogle Scholar
  18. 18.
    Cao J, Lou S, Ying M, et al. DJ-1 as a human oncogene and potential therapeutic target. Biochem Pharmacol, 2015,93(3):241–250CrossRefGoogle Scholar
  19. 19.
    Schumann C, Chan S, Khalimonchuk O, et al. Mechanistic Nanotherapeutic Approach Based on siRNA-Mediated DJ-1 Protein Suppression for Platinum-Resistant Ovarian Cancer. Mol Pharm, 2016,13(6):2070–2083CrossRefGoogle Scholar
  20. 20.
    Trivedi R, Dihazi GH, Eltoweissy M, et al. The antioxidant protein PARK7 plays an important role in cell resistance to Cisplatin-induced apoptosis in case of clear cell renal cell carcinoma. Eur J Pharmacol, 2016,784:99–110CrossRefGoogle Scholar
  21. 21.
    Sun WL, Chen J, Wang YP, et al. Autophagy protects breast cancer cells from epirubicin-induced apoptosis and facilitates epirubicin-resistance development. Autophagy, 2011,7(9):1035–1044CrossRefGoogle Scholar
  22. 22.
    Ismail IA, Kang HS, Lee HJ, et al. 2'-Benzoyloxycinnamaldehyde-mediated DJ-1 upregulation protects MCF-7 cells from mitochondrial damage. Biol Pharm Bull, 2012,35(6):895–902CrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology 2018

Authors and Affiliations

  • Xue-kai Pan
    • 1
  • Fei Su
    • 2
  • Li-hua Xu
    • 1
  • Zhang-shuo Yang
    • 1
  • Dan-wen Wang
    • 1
  • Li-jie Yang
    • 1
  • Fan-zheng Kong
    • 1
  • Wei Xie
    • 1
  • Mao-hui Feng
    • 1
  1. 1.Department of Gastrointestinal SurgeryZhongnan Hospital of Wuhan UniversityWuhanChina
  2. 2.Department of Oncologythe First Hospital of Lanzhou UniversityLanzhouChina

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