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Article

Upregulation of Stat1-HDAC4 confers resistance to etoposide through enhanced multidrug resistance 1 expression in human A549 lung cancer cells

Retraction in: /10.3892/mmr.2025.13461
  • Authors:
    • Chutima Kaewpiboon
    • Ratakorn Srisuttee
    • Waraporn Malilas
    • Jeong Moon
    • Sangtaek Oh
    • Hye Gwang Jeong
    • Randal N. Johnston
    • Wanchai Assavalapsakul
    • Young‑Hwa Chung
  • View Affiliations / Copyright

    Affiliations: Department of Biology, Faculty of Science, Thaksin University, Phatthalung 93110, Thailand, BK21+, Department of Cogno‑Mechatronics Engineering, Pusan National University, Busan 609‑735, Republic of Korea, Department of Advanced Fermentation Fusion Science and Technology, Kookmin University, Seoul 136‑702, Republic of Korea, Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305‑764, Republic of Korea, Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB T2N4N1, Canada, Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
  • Pages: 2315-2321
    |
    Published online on: November 14, 2014
       https://doi.org/10.3892/mmr.2014.2949
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Abstract

Despite efforts to develop efficient chemotherapeutic drug strategies to treat cancer, acquired drug resistance is a commonly encountered problem. In the present study, to investigate this phenomenon, human A549 lung cancer cells resistant to the topoisomerase inhibitor etoposide (A549RT‑eto) were used and compared with A549 parental cells. A549RT‑eto cells demonstrated increased resistance to etoposide‑induced apoptosis when compared with A549 parental cells. Notably, A549RT‑eto cells were observed to exhibit greater levels of histone deacetylase 4 (HDAC4), phospho‑Stat1 and P‑glycoprotein [P‑gp; encoded by the multidrug resistance 1 (MDR1) gene], compared with A549 cells. To address whether HDAC4 protein is involved in etoposide resistance in A549 cells, A549RT‑eto cells were treated with trichostatin A (TSA; an HDAC inhibitor) during etoposide treatment. The combined treatment was demonstrated to enhance etoposide‑induced apoptosis and reduce expression levels of HDAC4, P‑gp and phospho‑Stat1. In addition, the suppression of Stat1 with siRNA enhanced etoposide‑induced apoptosis and reduced the expression levels of HDAC4 and P‑gp, suggesting that Stat1 is essential in the regulation of resistance to etoposide, and in the upregulation of P‑gp. Notably, TSA treatment reduced P‑gp transcript levels but Stat1 siRNA treatment did not, suggesting that P‑gp is regulated by HDAC at the transcriptional level and by Stat1 at the post‑transcriptional level. These results suggest that the upregulation of Stat1 and HDAC4 determines etoposide resistance through P‑gp expression in human A549 lung cancer cells.
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Copy and paste a formatted citation
Spandidos Publications style
Kaewpiboon C, Srisuttee R, Malilas W, Moon J, Oh S, Jeong HG, Johnston RN, Assavalapsakul W and Chung YH: Upregulation of Stat1-HDAC4 confers resistance to etoposide through enhanced multidrug resistance 1 expression in human A549 lung cancer cells Retraction in /10.3892/mmr.2025.13461. Mol Med Rep 11: 2315-2321, 2015.
APA
Kaewpiboon, C., Srisuttee, R., Malilas, W., Moon, J., Oh, S., Jeong, H.G. ... Chung, Y. (2015). Upregulation of Stat1-HDAC4 confers resistance to etoposide through enhanced multidrug resistance 1 expression in human A549 lung cancer cells Retraction in /10.3892/mmr.2025.13461. Molecular Medicine Reports, 11, 2315-2321. https://doi.org/10.3892/mmr.2014.2949
MLA
Kaewpiboon, C., Srisuttee, R., Malilas, W., Moon, J., Oh, S., Jeong, H. G., Johnston, R. N., Assavalapsakul, W., Chung, Y."Upregulation of Stat1-HDAC4 confers resistance to etoposide through enhanced multidrug resistance 1 expression in human A549 lung cancer cells Retraction in /10.3892/mmr.2025.13461". Molecular Medicine Reports 11.3 (2015): 2315-2321.
Chicago
Kaewpiboon, C., Srisuttee, R., Malilas, W., Moon, J., Oh, S., Jeong, H. G., Johnston, R. N., Assavalapsakul, W., Chung, Y."Upregulation of Stat1-HDAC4 confers resistance to etoposide through enhanced multidrug resistance 1 expression in human A549 lung cancer cells Retraction in /10.3892/mmr.2025.13461". Molecular Medicine Reports 11, no. 3 (2015): 2315-2321. https://doi.org/10.3892/mmr.2014.2949
Copy and paste a formatted citation
x
Spandidos Publications style
Kaewpiboon C, Srisuttee R, Malilas W, Moon J, Oh S, Jeong HG, Johnston RN, Assavalapsakul W and Chung YH: Upregulation of Stat1-HDAC4 confers resistance to etoposide through enhanced multidrug resistance 1 expression in human A549 lung cancer cells Retraction in /10.3892/mmr.2025.13461. Mol Med Rep 11: 2315-2321, 2015.
APA
Kaewpiboon, C., Srisuttee, R., Malilas, W., Moon, J., Oh, S., Jeong, H.G. ... Chung, Y. (2015). Upregulation of Stat1-HDAC4 confers resistance to etoposide through enhanced multidrug resistance 1 expression in human A549 lung cancer cells Retraction in /10.3892/mmr.2025.13461. Molecular Medicine Reports, 11, 2315-2321. https://doi.org/10.3892/mmr.2014.2949
MLA
Kaewpiboon, C., Srisuttee, R., Malilas, W., Moon, J., Oh, S., Jeong, H. G., Johnston, R. N., Assavalapsakul, W., Chung, Y."Upregulation of Stat1-HDAC4 confers resistance to etoposide through enhanced multidrug resistance 1 expression in human A549 lung cancer cells Retraction in /10.3892/mmr.2025.13461". Molecular Medicine Reports 11.3 (2015): 2315-2321.
Chicago
Kaewpiboon, C., Srisuttee, R., Malilas, W., Moon, J., Oh, S., Jeong, H. G., Johnston, R. N., Assavalapsakul, W., Chung, Y."Upregulation of Stat1-HDAC4 confers resistance to etoposide through enhanced multidrug resistance 1 expression in human A549 lung cancer cells Retraction in /10.3892/mmr.2025.13461". Molecular Medicine Reports 11, no. 3 (2015): 2315-2321. https://doi.org/10.3892/mmr.2014.2949
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