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Licensed Unlicensed Requires Authentication Published by De Gruyter August 9, 2021

Lefty A is involved in sunitinib resistance of renal cell carcinoma cells via regulation of IL-8

Ning Cui, Qiang Han, Qizhen Cao, Kejun Wang, Xujia Zhou, Pingzhi Hou, Chao Liu, Lungang Chen and Lin Xu
From the journal Biological Chemistry


Renal cell carcinoma (RCC) is the third most frequent malignancy within urological oncology. Sunitinib has been used as the standard of treatment for first-line RCC therapy. Understanding mechanisms of sunitinib resistance in RCC cell is important for clinical therapy and drug development. We established sunitinib resistant RCC cells by treating cells with increasing concentrations of sunitinib and named resistant cells as RCC/SR. Lefty A, an important embryonic morphogen, was increased in RCC/SR cells. Targeted inhibition of Lefty via its siRNAs restored the sensitivity of renal resistant cells to sunitinib treatment. It was due to that si-Lefty can decrease the expression of interleukin-8 (IL-8) in RCC/SR cells. Knockdown of IL-8 abolished Lefty-regulated sunitinib sensitivity of RCC cells. Mechanistically, Lefty can regulate IL-8 transcription via activation of p65, one major transcription factor of IL-8. Collectively, our present revealed that Lefty A can regulate sunitinib sensitivity of RCC cells of via NF-κB/IL-8 signals. It indicated that targeted inhibition of Lefty might be a potent approach to overcome sunitinib resistance of RCC.

Keywords: IL-8; Lefty; RCC; sunitinib

Corresponding author: Ning Cui, Medical Imaging Center, Taihe Hospital, No.32 Renmin South Road, Shiyan 442000, Hubei Province, China, E-mail:
Ning Cui and Qiang Han contributed equally to this work.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Conflict of interest statement: The authors declare no conflict of interest.

  4. Consent for publication: All authors give the consent for the publish of this study.

  5. Availability of data and material: All data and material are available.


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Received: 2021-04-25
Accepted: 2021-06-23
Published Online: 2021-08-09
Published in Print: 2021-09-27

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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