Open Access

SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF‑κB pathway

  • Authors:
    • Shuangxi Gong
    • Lixin Xiong
    • Zhen Luo
    • Qinghua Yin
    • Ming Huang
    • Yang Zhou
    • Jian Li
  • View Affiliations

  • Published online on: June 8, 2022     https://doi.org/10.3892/etm.2022.11430
  • Article Number: 502
  • Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pancreatic cancer (PC) is a malignant tumor with high mortality worldwide. SIRT6 plays versatile roles in human cancers. However, SIRT6 has rarely been studied in PC. The purpose of the present study was to explore the function and potential mechanism of SIRT6 in PC. The expression of SIRT6 in PC tissues and cells was detected by reverse transcription‑quantitative PCR and western blotting. The overall survival time was analyzed through the Kaplan Meier method. Cell viability was measured by the Cell Counting Kit‑8 assay. The Fe2+ content, glucose uptake, lactic acid and ATP production were detected through the corresponding kits. ROS was evaluated using the DCFH‑DA detection kit. Protein expression was assessed by immunohistochemistry or western blot analysis. In the present study, SIRT6 was lowly expressed in PC tissues and cells compared with normal tissues and cells. Moreover, the low expression of SIRT6 was associated with a poor prognosis in patients with PC. Upregulation of SIRT6 significantly promoted the ferroptosis and inhibited the glycolysis in PC cells. However, knockdown of SIRT6 resisted ferroptosis and increased glycolysis in PC cells. Further studies found that the activation of NF‑κB could reverse the effect of SIRT6 on PC cells. In addition, overexpression of SIRT6 restrained the growth of xenografted tumors and suppressed the nuclear transcription of NF‑κB in vivo. Collectively, the present study indicated that SIRT6 promoted ferroptosis and inhibited glycolysis through inactivating the NF‑κB signaling pathway in PC. These findings suggested that SIRT6 may become a therapeutic target for PC.
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August-2022
Volume 24 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Gong S, Xiong L, Luo Z, Yin Q, Huang M, Zhou Y and Li J: SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF‑κB pathway. Exp Ther Med 24: 502, 2022
APA
Gong, S., Xiong, L., Luo, Z., Yin, Q., Huang, M., Zhou, Y., & Li, J. (2022). SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF‑κB pathway. Experimental and Therapeutic Medicine, 24, 502. https://doi.org/10.3892/etm.2022.11430
MLA
Gong, S., Xiong, L., Luo, Z., Yin, Q., Huang, M., Zhou, Y., Li, J."SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF‑κB pathway". Experimental and Therapeutic Medicine 24.2 (2022): 502.
Chicago
Gong, S., Xiong, L., Luo, Z., Yin, Q., Huang, M., Zhou, Y., Li, J."SIRT6 promotes ferroptosis and attenuates glycolysis in pancreatic cancer through regulation of the NF‑κB pathway". Experimental and Therapeutic Medicine 24, no. 2 (2022): 502. https://doi.org/10.3892/etm.2022.11430