Title:Development of a Lung Cancer Model in Wistar Rat and In Silico Screening of its Biomarkers
Volume: 17
Issue: 3
Author(s): Nisat Alam, Hasina Najnin, Maidul Islam, Saleem Iqbal and Rana Zaidi*
Affiliation:
- Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, 110062,India
Keywords:
Lung cancer, NNK, male Wistar rats, histopathology, molecular docking, EGFR.
Abstract:
Background: Cancer is usually caused by three factors: Nutrition, inflammation and cigarette
smoke. This study on rat experimental models would enable us to understand the mechanism
of lung cancer caused by NNK to which humans are continuously exposed, help us understand possible
molecular targets, and assist in designing drugs for humans against lung cancer.
Aim: A lung cancer model was developed by administering tobacco-specific carcinogen: NNK [4-
methylnitrosamino)-1-(3-pyridyl)-1-butanone] to male Wistar rats for 24 weeks. Furthermore, in
silico approach was followed to screen the molecular targets.
Methods: A method was established in which subcutaneous and intraperitoneal injections of NNK
were administered to male Wistar rats simultaneously. For authentication of lung cancer in vivo, we
performed molecular docking simulations with protein biomarkers: Cox-2, p53, p38 MAPKs and
EGFR using Hex-Discovery Studio, Schrödinger-maestro software.
Results: Lung morphology and histopathology indicated the initiation of bronchiolar epithelial hyperplasia
and squamous dysplasia in the cancer 1 group after 16 weeks of NNK exposure. 66.66%
incidence of squamous cell carcinoma (SCC) and 33.3% incidence of adenocarcinoma were observed
in cancer 2 group after being exposed to NNK. Results indicated that the incidence of SCC
and adenocarcinoma gradually increased from 66.66% to 85.71% in cancer 2 group and from
33.33% to 42.58% in cancer 3 group, respectively. Docking results indicate the total binding energy
and glide energy of Cox-2, p53, p38 MAPKs, EGFR : 38.14, -211.58, -181.58, -213.05 Kcal/mol
and -39.25, -32.16,-36.49, -40.19 Kcal/mol, respectively.
Conclusion: Pulmonary adenocarcinoma model was developed by administering tobacco-specific
carcinogen: NNK [4-methylnitrosamino)-1-(3-pyridyl)-1-butanone] to male Wistar rats in 24
weeks. In silico experiments confirmed EGFR to be the most potential target for NNK induced lung
Cancer.
