Investigational New Drugs

, Volume 28, Issue 3, pp 205–215 | Cite as

Augmented antitumor effects of combination therapy of cisplatin with ethaselen as a novel thioredoxin reductase inhibitor on human A549 cell in vivo



Ethaselen (1, 2-[bis (1, 2-Benzisoselenazolone-3 (2H) -ketone)] ethane, BBSKE), as a novel organoselenium compound targeting thioredoxin reductase (TrxR), has been reported to inhibit tumor growth and TrxR activity in several human tumor cell lines. It has now entered Phase I clinical trails. Here we report the effects of ethaselen and cisplatin (cis-diamminedichloroplatinum II, DDP) combination therapy (ethaselen 36 mg/kg, i.g., o.d. × 10 d and cisplatin 1 mg/kg, i.p., single at day 0) on human A549-grafted nude mouse model (female, BALB/c nude mouse, n = 5, treatment after tumor volume reached 100 mm3). Compared to single drug administration (either ethaselen: 36 mg/kg, i.g., o.d. × 10 d or cisplatin: 1.0 mg/kg, i.p., single at day 0), the combination therapy showed significantly reduced tumor size (presumably due to a synergistic effect) and no obvious toxic damage (both in terms of body weight maintenance and liver/kidney damage). These results will be significant in the development of novel anti-tumoral therapeutic strategies directed to non-small cell lung cancer (NSCLC).


Ethaselen Thioredoxin reductase inhibitor Cisplatin Non-small cell lung cancer Combination chemotherapy Synergistic effect 


Ethaselen (BBSKE)

1, 2-[bis (1,2-Benzisoselenazolone-3 (2H) -ketone)]ethane


Blood urea nitrogen




Hematoxylin eosin








No-observed adverse effect level


Non-small cell lung cancer


Specific pathogen free




Thioredoxin reductase



This work was supported in part by the National Natural Science Foundation of China (30472036).


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Qiang Tan
    • 1
    • 2
  • Jing Li
    • 1
  • Han-wei Yin
    • 3
  • Li-hui Wang
    • 1
  • Wan-chen Tang
    • 1
  • Fang Zhao
    • 1
  • Xin-min Liu
    • 2
  • Hui-hui Zeng
    • 1
    • 4
  1. 1.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical SciencesPeking UniversityBeijingChina
  2. 2.Peking University First HospitalBeijingChina
  3. 3.College of Life SciencesPeking UniversityBeijingChina
  4. 4.School of Pharmaceutical SciencesPeking University Health Science CenterBeijingChina

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