Background:
Cancer is caused by three factors: Nutrition, inflammation and cigarette
smoke. This study in 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, design 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 in 24 weeks.
Further, 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, squamous dysplasia beginning in cancer 1 group after 16 weeks NNK
exposure. 66.66% incidence of squamous cell carcinoma (SCC), 33.3% incidence of
adenocarcinoma in cancer 2 group after being exposed to NNK. Results indicated that the
SCC and adenocarcinoma gradually increased from 66.66% to 85.71% in cancer 2 group and
33.33% to 42.58% in cancer 3 groups 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 developed in 24 weeks, in silico experiments
confirm EGFR to be the most potential target for NNK induced lung Cancer.
Lung flooding enables efficient lung sonography and tumour imaging in human ex vivo and porcine in vivo lung cancer model