Abstract：
The majority of adenocarcinoma lung cancer is found in nonsmokers. A history of tobacco use is more common in squamous cell carcinoma of the lung. The aim of this study is to identify the cisplatin (CDDP)-resistance that promotes lung squamous carcinoma cell growth through nicotine-mediated HDAC1/7nAchR/E2F/pRb cell cycle activation. Squamous cell carcinoma (NCI-H520 and NCI-H157) cells were examined after cisplatin and nicotine treatment by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, cell migration assay, immunofluorescence staining, western blot analysis, and immunoprecipitation analysis. Consequently, CDDP is released from DNA and Rb phosphorylated pRb as a result of nicotine-induced cancer cell proliferation through 7nAchR, which then triggers the opening of the HDAC1 cell cycle. The cell cycle is stopped when CDDP adducts are present. Nicotine exerts cancer cytoprotective effects by allowing HDAC1 repair mechanisms to re-establish E2F promoting DNA stimulation cell cycle integrity in the cytosol and preventing potential CDDP and HDAC1 suppressed in the nuclear. Concentration expression of nicotine causes squamous carcinoma cell carcinogens to emerge from inflammation. COX2, NF-KB, and NOS2 increase as a result of nicotine-induced squamous carcinoma cell inflammation. Nicotine enhanced the cell growth-related proteins such as α7nAchR, EGFR, HDAC1, Cyclin D, Cyclin E, E2F, Rb, and pRb by western blot analysis. It also induced cancer cell inflammation and growth. As a result, we suggest that nicotine will increase the therapeutic resistance effects of CDDP. This has the potential to interact with nicotine through α7nAchR receptors and HDAC1/Cyclin D/E2F/pRb potentially resulting in CDDP therapy resistance, as well as cell cycle-induced cancer cell growth.
摘要：
大多数腺癌肺癌见于非吸烟者。烟草使用史在肺鳞状细胞癌中更常见。这项研究的目的是通过尼古丁介导的HDAC1/7nAchR/E2F/pRb细胞周期激活来确定促进肺鳞状癌细胞生长的顺铂（CDDP）耐药性。顺铂和尼古丁处理后，通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基-2H-四唑溴化物测定法检查鳞状细胞癌（NCI-H520和NCI-H157）细胞，细胞迁移试验，免疫荧光染色，蛋白质印迹分析,和免疫沉淀分析。因此,由于尼古丁通过7nAchR诱导的癌细胞增殖，CDDP从DNA中释放，Rb磷酸化pRb，然后触发HDAC1细胞周期的开启。当CDDP加合物存在时,细胞周期停止。尼古丁通过允许HDAC1修复机制重新建立E2F来发挥癌症细胞保护作用，从而促进细胞质中DNA刺激细胞周期的完整性，并防止核中潜在的CDDP和HDAC1被抑制。尼古丁的浓度表达导致鳞状癌细胞致癌物从炎症中出现。COX2,NF-KB,尼古丁诱导的鳞状癌细胞炎症导致NOS2增加。尼古丁增强了细胞生长相关蛋白，如α7nAchR，EGFR,HDAC1,细胞周期蛋白D,细胞周期蛋白E,E2F,Rb,和pRb通过蛋白质印迹分析。它还诱导癌细胞炎症和生长。因此,我们认为尼古丁会增加CDDP的治疗耐药性。这有可能通过α7nAchR受体和HDAC1/CyclinD/E2F/pRb与尼古丁相互作用，可能导致CDDP治疗抵抗，以及细胞周期诱导的癌细胞生长。
