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- 2019
脂肪旁分泌介导肥胖对食管鳞癌细胞生物学行为的影响
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Abstract:
摘要:目的 明确肥胖与食管鳞癌之间的关系并阐述其相关分子机制。方法 通过内脏脂肪组织体外培养获得条件培养基从而模拟脂肪旁分泌过程,进而培养食管鳞癌细胞,通过MTT、流式细胞仪、RT-PCR、Western blot等途径分析内脏脂肪旁分泌介导肥胖对食管鳞癌细胞增殖、凋亡、细胞周期及相关基因表达等的影响。结果 与非肥胖组相比,肥胖组Eca109细胞增殖明显增加(P<0.05);细胞凋亡率明显减少[(18.63±3.69)% vs. (29.97±2.00)%, P<0.05];细胞周期中S期增加(P<0.05)、G0/G1期减少(P<0.05);AMPK、磷酸化YAP蛋白表达下降(P<0.05),总YAP蛋白表达升高(P<0.05);AMPK mRNA表达下降(P<0.05),YAP mRNA表达升高(P<0.05)。 结论 肥胖通过内脏脂肪旁分泌方式改变食管鳞癌细胞生物学行为并调控与糖脂代谢、肿瘤生长密切相关的AMPK-YAP信号通路。
ABSTRACT: Objective To clarify the relationship between obesity and esophageal squamous cell carcinoma so as to elucidate the molecular mechanisms involved. Methods Conditioned medium was obtained by culturing visceral adipose tissue in vitro for simulating the paracrine process of visceral adipose tissue, and then used to culture esophageal squamous cell carcinoma cells. MTT, flow cytometry, RT-PCR and Western blot were used to analyze the paracrine effects of visceral adipose tissue on proliferation, apoptosis, cell cycle and related genes expression of esophageal squamous cell carcinoma cells. Results Compared with those in non-obese group, the proliferation of Eca109 cells in obese group was significantly increased (P<0.05); the percentage of apoptotic cells was significantly decreased [(18.63±3.69)% vs. (29.97±2.00)%, P<0.05)]; S phase was significantly increased (P<0.05) while G0/G1 phase was significantly declined (P<0.05); the expressions of AMPK and phosphorylated YAP protein was significantly decreased (P<0.05); the total level of YAP protein was significantly increased (P<0.05); the mRNA expression of AMPK was significantly decreased (P<0.05) while YAP mRNA expression increased significantly (P<0.05) in obese group. Conclusion Obesity affects the biological behavior of esophageal squamous carcinoma cells and regulates the AMPK-YAP signaling pathway that is closely related to glucose and lipid metabolism and tumor growth through the paracrine pathway of visceral adipose tissue