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Preliminary evaluation of anticancer efficacy of pioglitazone combined with celecoxib for the treatment of non-small cell lung cancer

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Summary

Purpose. Among the lung cancer types, non-small cell lung cancer (NSCLC) is prominent and less responsive to chemotherapy. The current chemotherapeutics for NSCLC are associated with several dose-limiting side effects like bone-marrow suppression, neurotoxicity, nephrotoxicity, and ototoxicity, etc. which are causing non-compliance in patients. Many tumors, including breasts, lung, ovarian, etc. overexpress PPAR-γ receptors and COX-2 enzymes, which play a crucial role in tumor progression, angiogenesis, and metastasis. Lack of PPAR-γ activation and overproduction of prostaglandins, result in uncontrolled activation of Ras/Raf/Mek ultimately, NF-κB mediated tumor proliferation. This study aimed to investigate the anti-cancer potential of PPAR-γ agonist Pioglitazone combined with COX-2 inhibitor Celelcoxib in NSCLC. Methods. Sixty adult Balb/C male mice were classified into sham control, disease control, and treatment groups. Mice were treated with Nicotine-derived nitrosamine ketone (NNK) (10 mg/kg), pioglitazone (10 & 20 mg/kg) and celecoxib (25 & 50 mg/kg). Weekly body weight, food intake, mean survival time & % increased life span were determined. Tumor weight and histopathological analysis were performed at the end of the study. Results. The significant tumor reducing potential of pioglitazone combined with celecoxib was observed (p < 0.05). The treatment groups (treated with pioglitazone and celecoxib) showed a remarkable decrease in lung tumor weight, improved life span and mean survival time (p < 0.05). Histopathological studies confirm that treatment groups (treated with pioglitazone and celecoxib) reframed the lung architecture compared to disease control. Conclusion. Preliminary results revealed that pioglitazone adjunacy with celecoxib may be an effective chemo-preventive agent against NNK induce NSCLC.

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Acknowledgements

I would like to thank Dr. Praveen T.K. for his continuous guidance and support throughout this project. My sincere thanks to Ms. Kusuma Kumari for her suggestions and help in performing the experiment and preparing the manuscript.

Funding

The authors would like to thank the Department of Science and Technology-Fund for Improvement of Science and Technology Infrastructure in Universities and Higher Educational Institutions (DST-FIST), New Delhi, to support our department (Grant No. SR/FST/LSI-574/2013).

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Authors and Affiliations

  1. Department of Pharmacology, JSS College of Pharmacy (JSS Academy of Higher Education & Research) Rocklands, Ooty, The Nilgiris, Tamil Nadu, 643001, India

    Ammu V. V. V. Ravi Kiran, Garikapati Kusuma Kumari & Praveen T. Krishnamurthy

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Contributions

PTK and AVVVRK generated hypothesis. PTK helped in conceptualization, supervision, validation and proof reading. AVVVRK has conceptualized, carriedout the work, data analysis, writing-original draft; GKK validated and proof-read the manuscript.

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Correspondence to Praveen T. Krishnamurthy.

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The experiment was performed with prior approval from the Institutional Animal Ethics Committee (IAEC) (Approval No. JSSCP/OT/M.PHARM/05/18–19).

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Kiran, A.V.V.V.R., Kumari, G.K. & Krishnamurthy, P.T. Preliminary evaluation of anticancer efficacy of pioglitazone combined with celecoxib for the treatment of non-small cell lung cancer. Invest New Drugs 40, 1–9 (2022). https://doi.org/10.1007/s10637-021-01158-7

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