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The Effect of TIGAR Knockdown on Apoptotic and Epithelial-Mesenchymal Markers Expression in Doxorubicin-Resistant Non-Small Cell Lung Cancer A549 Cell Lines

Agca, Can Ali; Kirici, Mahinur; Nedzvetsky, Victor S.; Gundogdu, Ramazan; Tykhomyrov, Artem A.


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{
  "DOI": "10.1002/cbdv.202000441", 
  "abstract": "Resistance to chemotherapeutic drugs is a critical problem in cancer therapy, but the underlying mechanism has not been fully elucidated. TP53-induced glycolysis regulatory phosphatase (TIGAR), an important glycolysis and apoptosis regulator, plays a crucial role in cancer cell survival by protecting cells against oxidative stress-induced apoptosis. In the present study, we investigated whether TIGAR is involved in epithelial-mesenchymal transition (EMT) in doxorubicin (DOX)-resistant human non-small cell lung cancer (NSCLC), A549/DOX cells. We found that the expression of TIGAR was significantly higher in A549/DOX cells than in the parent A549 cell lines. siRNA-mediated TIGAR knockdown reduced migration, viability and colony survival of doxorubicin-resistant lung cancer cells. Also, TIGAR knockdown decreased pro-survival protein Bcl-2 and increased pro-apoptotic Bax and cleaved poly (ADP-ribose) polymerase (PARP). Moreover, TIGAR depletion significantly up-regulated both caspase-3 and caspase-9 expression. Furthermore, TIGAR depletion up-regulated the expression of E-cadherin and down-regulated the expression of vimentin. These results indicate that TIGAR knockdown may inhibit EMT in doxorubicin (DOX)-resistant human NSCLC and may represent a therapeutic target for a non-small lung cancer cells chemoresistance.", 
  "author": [
    {
      "family": "Agca", 
      "given": " Can Ali"
    }, 
    {
      "family": "Kirici", 
      "given": " Mahinur"
    }, 
    {
      "family": "Nedzvetsky", 
      "given": " Victor S."
    }, 
    {
      "family": "Gundogdu", 
      "given": " Ramazan"
    }, 
    {
      "family": "Tykhomyrov", 
      "given": " Artem A."
    }
  ], 
  "container_title": "CHEMISTRY & BIODIVERSITY", 
  "id": "10957", 
  "issue": "9", 
  "issued": {
    "date-parts": [
      [
        2020, 
        1, 
        1
      ]
    ]
  }, 
  "title": "The Effect of TIGAR Knockdown on Apoptotic and Epithelial-Mesenchymal Markers Expression in Doxorubicin-Resistant Non-Small Cell Lung Cancer A549 Cell Lines", 
  "type": "article-journal", 
  "volume": "17"
}
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