Cellular Oncology

, Volume 35, Issue 6, pp 461–471 | Cite as

High expression of heme oxygenase-1 is associated with tumor invasiveness and poor clinical outcome in non-small cell lung cancer patients

  • Jong-Rung Tsai
  • Hui-Min Wang
  • Po-Len Liu
  • Yung-Hsiang Chen
  • Ming-Chan Yang
  • Shah-Hwa Chou
  • Yu-Jen Cheng
  • Wei-Hsian Yin
  • Jhi-Jhu Hwang
  • Inn-Wen Chong
Original Papers



Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, is known to play a role in the protection of cells against oxidative stress, inflammation, anomalous proliferation and apoptosis. As yet, the role of HO-1 expression in non-small cell lung cancer (NSCLC) development and metastasis remains unclear and insufficient data are available regarding its impact on the prognosis of NSCLC patients.


Seventy NSCLC patients who underwent surgical resection were included in this HO-1 expression study and, concomitantly, clinical parameters were collected. Two lung adenocarcinoma cell lines (A549 and H441) were used to assess both invasive and migratory parameters in vitro.


NSCLC patients with a high HO-1 expression ratio (tumor tissue/normal tissue) (> 1) exhibited a significantly poorer prognosis and a higher metastatic rate compared to those with a low HO-1 expression ratio (p < 0.05). The invasive and migratory abilities of A549 and H441 cells significantly increased after exogenous HO-1 over-expression and significantly decreased after siRNA-mediated HO-1 expression silencing. HO-1 up- and down-regulation also positively correlated with the expression of metastasis-associated proteins EGFR, CD147 and MMP-9. In addition, we found that HO-1 expression can be inhibited by PI3K and AKT inhibitors, but not by MAPK inhibitors.


HO-1 is a poor prognostic NSCLC predictor and its over-expression may increase the metastatic potential of NSCLC. Based on our findings and those of others, HO-1 may be considered as a novel NSCLC therapeutic target.


Heme Oxygenase-1 Metastasis Prognosis Non-small cell lung cancer 



This study was supported by grants from the National Science Council, grants NSC NSC99-2314-B-037-058-MY2 and NSC 100-2320-B-039-008-MY2, Kaohsiung Medical University Hospital grant KMUH99-9 M64, and Kaohsiung Medical University grant KMU-Q098022, Taiwan.

Disclosure/state of interest

The authors declare that they have no competing interests.


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Copyright information

© International Society for Cellular Oncology 2012

Authors and Affiliations

  • Jong-Rung Tsai
    • 1
    • 2
  • Hui-Min Wang
    • 3
  • Po-Len Liu
    • 1
  • Yung-Hsiang Chen
    • 4
  • Ming-Chan Yang
    • 5
  • Shah-Hwa Chou
    • 1
    • 6
  • Yu-Jen Cheng
    • 7
  • Wei-Hsian Yin
    • 8
  • Jhi-Jhu Hwang
    • 1
    • 2
  • Inn-Wen Chong
    • 1
    • 2
  1. 1.Department of Respiratory TherapyCollege of Medicine, Kaohsiung Medical UniversityKaohsiungTaiwan
  2. 2.Department of Internal MedicineKaohsiung Medical University HospitalKaohsiungTaiwan
  3. 3.Department of Fragrance and Cosmetic ScienceKaohsiung Medical UniversityKaohsiungTaiwan
  4. 4.Graduate Institute of Integrated Medicine, College of Chinese Medicine, Department of UrologyChina Medical University and HospitalTaichungTaiwan
  5. 5.Department of SurgeryYuan’s General HospitalKaohsiungTaiwan
  6. 6.Department of Surgery, Division of Chest SurgeryKaohsiung Medical University HospitalKaohsiungTaiwan
  7. 7.Department of Health Management, Division of Thoracic SurgeryDepartment of Surgery, E-Da Hospital, I-Shou UniversityKaohsiungTaiwan
  8. 8.Division of CardiologyCheng-Hsin General Hospital, Faculty of Medicine, and Cardiovascular Research Centre, School of Medicine, National Yang-Ming UniversityTaipeiTaiwan

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