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Inflammopharmacology

, Volume 27, Issue 1, pp 89–98 | Cite as

Antineoplastic influence of nimesulide in chemically induced hepatocellular carcinoma by inhibition of DNA synthesis

  • M. Afzal
  • D. P. Bhardwaj
  • R. Khan
  • Imran KazmiEmail author
  • S. Saleem
  • F. A. Al-Abbasi
  • Firoz AnwarEmail author
Original Article

Abstract

Hepatocellular carcinoma is emerging as one of the most common forms of cancer resulting in thousands of death worldwide. The purpose of this study was to screen nimesulide for anticancer activity in chemically induced hepatocellular carcinoma in Wistar rats as well as in BEL 7402 and HEP G2 cell lines. HCC in rats was induced by administering a single dose of diethyl nitrosamine (150 mg/kg) intraperitoneally. Duration of the in vivo study was 12 weeks and the anticancer potential was further confirmed by in vitro cell line study. Administration of DENA in Wistar rats significantly elevated the levels of serum biochemical parameters and α-feto protein. Treatment with different dose of nimesulide significantly decreased the markedly raised serum levels of biochemical parameters as well as maintained the histology of the liver tissues nearly similar to the normal. Further study of hepatocytes enzymes showed that treatment with nimesulide also improved the antioxidant enzyme levels. Our study also examined the cytotoxicity and DNA synthesis inhibition by nimesulide in BEL 7402 and Hep G2 cell lines. Cell viability was assessed by [3H]-thymidine uptake procedure. The results obtained by in vitro cell line study, histopathological and biochemical data concluded that nimesulide, a preferential COX-2 inhibitor, has anticancer activity, which is by first reducing the formation of reactive oxygen species and second by inhibiting the PGE2 effect via Wnt signaling pathway (cell invasion, angiogenesis, and cell proliferation).

Keywords

COX-2 inhibitor Diethylnitrosamine Biochemical parameters Hepatoprotective 

Abbreviations

HCC

Hepatocellular carcinoma

ALP

Alkaline phosphatase

TBi

Total bilirubin

AFP

α-Feto protein

Notes

Acknowledgements

This research work was not funded by any organization.

Compliance with ethical standards

Conflict of interest

The author declares that there is no competing interest.

Compliance with ethics requirements

Manuscript is under compliance with ethical standard of journal.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmacology, College of PharmacyJouf UniversitySakakaKingdom of Saudi Arabia
  2. 2.Siddhartha Institute of PharmacyDehradunIndia
  3. 3.Glocal School of PharmacyGlocal UniversitySahranpurIndia
  4. 4.Department of Biochemistry, Faculty of ScienceKing Abdulaziz UniversityJeddahSaudi Arabia

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