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.

背景：癌症通常由三个因素引起：营养、炎症和香烟烟雾。这项对大鼠实验模型的研究将使我们能够了解人类持续暴露于 NNK 导致肺癌的机制，帮助我们了解可能的分子靶点，并有助于设计人类抗肺癌的药物。

目的：通过对雄性 Wistar 大鼠施用烟草特异性致癌物：NNK [4-甲基亚硝胺)-1-(3-吡啶基)-1-丁酮] 24 周来建立肺癌模型。此外，采用计算机方法来筛选分子靶标。

方法：建立了一种同时对雄性 Wistar 大鼠进行皮下和腹腔注射 NNK 的方法。为了在体内鉴定肺癌，我们使用 Hex-Discovery Studio、Schrödinger-maestro 软件对蛋白质生物标志物进行了分子对接模拟：Cox-2、p53、p38 MAPK 和 EGFR。

结果：肺形态学和组织病理学表明，在暴露于 NNK 16 周后，癌症 1 组开始出现细支气管上皮增生和鳞状细胞发育不良。在暴露于NNK后，癌症2组观察到66.66%的鳞状细胞癌（SCC）发生率和33.3%的腺癌发生率。结果表明，癌2组SCC和腺癌的发生率分别从66.66%逐渐增加到85.71%，癌3组从33.33%逐渐增加到42.58%。对接结果表明 Cox-2、p53、p38 MAPKs、EGFR 的总结合能和滑动能：38.14、-211.58、-181.58、-213.05 Kcal/mol 和 -39.25、-32.16、-36.49、-40.19 Kcal ， 分别。

结论：通过在 24 周内对雄性 Wistar 大鼠施用烟草特异性致癌物 NNK [4-甲基亚硝胺)-1-(3-吡啶基)-1-丁酮] 建立肺腺癌模型。计算机实验证实 EGFR 是 NNK 诱导肺癌的最潜在靶点。