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Darbufelone, a novel anti-inflammatory drug, induces growth inhibition of lung cancer cells both in vitro and in vivo

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Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Inflammation plays a crucial role in the development of lung cancer. Accumulated studies have proved that non-steroidal anti-inflammatory drugs (NSAIDs) which block inflammation by their actions on arachidonic acid (AA) metabolism have a potential role in cancer chemotherapy and chemoprevention. The aim of our study was to investigate whether darbufelone, a novel anti-inflammatory drug, has anticancer effects in lung cancer.

Methods

Human non-small cell lung cancer cell lines were treated with darbufelone at various doses and time points for analysis of cell viability, cell cycle, and apoptosis in vitro. The in vivo effect of darbufelone was assessed in Lewis lung carcinoma mice model.

Results

Darbufelone inhibited the proliferation of non-small cell lung cancer cell lines in a dose-dependent manner, and induced cell cycle arrest at G0/G1 phase through up-regulation of p27 expression. Treatment with darbufelone also induced apoptosis by activating caspase-3 and caspase-8. Lewis lung carcinoma growth was also significantly inhibited by darbufelone treatment at daily dose of 80 mg/kg.

Conclusions

Taken together, these studies suggested that darbufelone, an anti-inflammation drug, might represent a novel therapeutic approach for lung cancer treatment.

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Abbreviations

AA:

Arachidonic acid

COX-2:

Cyclooxygenase-2

5-LOX:

5-Lipoxygenase

Darbufelone:

Darbufelone mesilate

SCLC:

Small cell lung cancer

NSCLC:

Non-small cell lung cancer

RT:

Reverse transcriptase

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Acknowledgments

We appreciate the time and effort of Dr. Hongbin. Ji and Dr. Yan Ren in reviewing these manuscripts and we thank Li Li for technical support in IHC.

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Authors and Affiliations

  1. Department of Pharmacology, China Pharmaceutical University, 24 Tong Jia Xiang, 210009, Nanjing, People’s Republic of China

    Xiaolei Ye, Yongqi Li & Hui Ji

  2. Center of Drug Discovery, China Pharmaceutical University, 24 Tong Jia Xiang, 210009, Nanjing, People’s Republic of China

    Yihua Zhang & Yisheng Lai

  3. Institute of Immunology, Zhejiang University, 210058, Hangzhou, People’s Republic of China

    Wu Zhou

  4. Department of Thoracic Surgery, Shanghai Cancer Hospital, Fudan University, 20032, Shanghai, People’s Republic of China

    Yihua Sun

Authors
  1. Xiaolei Ye
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  2. Wu Zhou
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  3. Yongqi Li
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  4. Yihua Sun
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  5. Yihua Zhang
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  6. Hui Ji
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  7. Yisheng Lai
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Corresponding authors

Correspondence to Hui Ji or Yisheng Lai.

Additional information

X. Ye and W. Zhou contributed equally to this work.

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Ye, X., Zhou, W., Li, Y. et al. Darbufelone, a novel anti-inflammatory drug, induces growth inhibition of lung cancer cells both in vitro and in vivo. Cancer Chemother Pharmacol 66, 277–285 (2010). https://doi.org/10.1007/s00280-009-1161-z

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  • DOI: https://doi.org/10.1007/s00280-009-1161-z

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