Department of Surgery Pietro Valdoni, Sapienza University of Rome, Rome, Italy.
J Surg Res. 2012 Nov;178(1):233-41. doi: 10.1016/j.jss.2011.12.029. Epub 2012 Mar 10.
Colorectal cancer is one of the leading causes of cancer-related death throughout the world, and the risk to develop this malignant disease seems to be associated with long-term cigarette smoking. Nicotine, one of the major components of cigarette smoking, can stimulate cell proliferation and suppress apoptosis both in normal cells and in several human cancer cell lines derived from various organs. However, although nicotine appears to have a role in stimulating cell proliferation of colon cancer cells, there is no information on its role in inhibiting apoptosis in these cells.
Human colorectal cancer cell lines Caco-2 and HCT-8 were treated with 1 μM nicotine alone or in combination with 1 μM α-BTX in complete or in serum free medium. Cell proliferation and apoptosis were determined by cell count performed with a cell counter and by cytofluorimetric assay respectively. PI3K/Akt and PKC/ERK1/2 pathways, survivin, and P-Bcl2 (Ser70) were investigated by Western blot analysis.
Nicotine induced an increase in cell proliferation and a decrease of apoptosis in Caco-2 and HCT-8 cells. Both cell growth and apoptosis appear to be mediated by α7-nicotinic acetylcholine receptors, since treatment with α-Bungarotoxin inhibited these processes. Nicotine induced a statistically significant increase in the expression of PI3K and in P-Akt/Akt ratio as well as in the expression of PKC, ERK1/2, survivin, and P-Bcl2 (Ser70) in both cell lines.
Nicotine, contained in cigarette smoking, could participate in colon cancer development and progression by stimulating cell proliferation and suppressing physiological apoptosis.
结直肠癌是全世界癌症相关死亡的主要原因之一，而罹患这种恶性疾病的风险似乎与长期吸烟有关。香烟中的主要成分之一尼古丁，既能刺激正常细胞和多种源自不同器官的人类癌细胞系的细胞增殖，又能抑制这些细胞的凋亡。然而，尽管尼古丁似乎在刺激结肠癌细胞增殖方面发挥了作用，但关于其在抑制这些细胞凋亡方面的作用尚无信息。
用 1μM 尼古丁单独或与 1μM α-BTX 联合处理人结直肠癌细胞系 Caco-2 和 HCT-8，在完全培养基或无血清培养基中进行。用细胞计数器进行细胞计数和细胞流式术分别测定细胞增殖和细胞凋亡。用 Western blot 分析检测 PI3K/Akt 和 PKC/ERK1/2 通路、生存素和 P-Bcl2（Ser70）。
尼古丁诱导 Caco-2 和 HCT-8 细胞增殖增加和凋亡减少。细胞生长和凋亡似乎都由α7-烟碱型乙酰胆碱受体介导，因为用α-银环蛇毒素处理可抑制这些过程。尼古丁诱导两种细胞系中 PI3K 和 P-Akt/Akt 比值以及 PKC、ERK1/2、生存素和 P-Bcl2（Ser70）的表达均呈统计学显著增加。
香烟中含有的尼古丁，可能通过刺激细胞增殖和抑制生理性凋亡，参与结直肠癌的发生和发展。
