Abstract:Objective To investigate the effects of Butein on esophagus cancer EC109 cells and the role of AMP-activated protein kinase (AMPK)/forkhead class box O3a (FOXO3a) and oxidative stress in this process. Methods EC109 cell was routine cultured and given Butein, the cell vitality, migration ability, cellular oxidative stress level of EC109 cell and Caspase 3 activity were detected. The AMPK, FOXO3 aphosphorylation level and the expressions of Bim and Bax were detected by Western blot. After Compound C inhibit AMPK, related indicators were detected. The nude mice tumor bearing model was made, Butein and Compound C were given, the weight and tumor volume of nude mice were detected. Results After Butein treatment, cell vitality reduced, the distance between cell boundaries increased, ROS concentration and NADPH oxidase activity increased, total GSH level and Caspase 3 activity reduced (P < 0.05); AMPKand FOXO3 aphosphorylation and cell apoptosis increased (P < 0.05); Compound C treatment reversed this process. The nude mice tumor study showed that Butein inhibited the tumor growth and Compound C reversed this effect. Conclusion Butein can induce EC109 cell apoptosis, and this process may be mediated by activation of AMPK/FOXO3a and cellular oxidative stress.
[1] Gould JC,Wendling MR,Oeschlager BK,et al. Advances in the diagnosis and treatment of barrett's esophagus and early esophageal cancer; summary of the Kelly and carlos pellegrini SSAT/SAGES luncheon symposium [J]. J Gastrointest Surg, 2017. doi: 10.1007/s11605-017-3390-5. [Epub ahead of print]
[2] Ke L. Mortality and incidence trends from esophagus cancer in selected geographic areas of China circa 1970-90 [J]. Int J Cancer,2002,102(3):271-274.
[3] Wang FR,Fang QQ,Tang WM,et al. Nested case-control study of occupational radiation exposure and breast and esophagus cancer risk among medical diagnostic x ray workers in Jiangsu of China[J]. Asian Pac J Cancer Prev,2015,16(11):4699-4704.
[4] Padmavathi G,Rathnakaram SR,Monisha J,et al. Potential of butein,a tetrahydroxychalcone to obliterate cancer [J]. Phytomedicine,2015,22(13):1163-1171.
[5] Bai X,Ma Y,Zhang G. Butein suppresses cervical cancer growth through the PI3K/AKT/mTOR pathway [J]. Oncol Rep,2015,33(6):3085-3092.
[6] Cho SG,Woo SM,Ko SG. Butein suppresses breast cancer growth by reducing a production of intracellular reactive oxygen species [J]. J Exp Clin Cancer Res,2014,33:51.
[7] Jung SK,Lee MH,Lim DY,et al. Butein,a novel dual inhibitor of MET and EGFR,overcomes gefitinib-resistant lung cancer growth [J]. Mol Carcinog,2015,54(4):322-331.
[8] Wang Z,Wang N,Liu P,et al. AMPK and Cancer [J]. EXS,2016,107:203-226.
[9] Zhou C,Gu J,Zhang G,et al. AMPK-autophagy inhibition sensitizes icaritin-induced anti-colorectal cancer cell activity [J]. Oncotarget,2017,8(9):14736-14747.
[10] 张志强,杨艳荣,李运霞.肺癌组织及其肺癌干细胞中FOXO3的表达及意义[J].临床与实验病理学杂志,2015, 31(8):880-884.
[11] Banskota S,Regmi SC,Kim JA. NOX1 to NOX2 switch deactivates AMPK and induces invasive phenotype in colon cancer cells through overexpression of MMP-7 [J]. Mol Cancer,2015,14:123.
[12] 刘鑫,胡皆乐,李佑,等.FOXO3在结直肠癌组织中的表达及临床意义[J].实用癌症杂志,2016,31(11):1773-1777.
[13] Chaube B,Bhat MK. AMPK,a key regulator of metabolic/energy homeostasis and mitochondrial biogenesis in cancer cells [J]. Cell Death Dis,2016,7:e2044.
[14] Davila D,Connolly NM,Bonner H,et al. Two-step activation of FOXO3 by AMPK generates a coherent feed-forward loop determining excitotoxic cell fate [J]. Cell Death Differ,2012,19(10):1677-1688.
[15] Li XN,Song J,Zhang L,et al. Activation of the AMPK-FOXO3 pathway reduces fatty acid-induced increase in intracellular reactive oxygen species by upregulating thioredoxin [J]. Diabetes,2009,58(10):2246-2257.
[16] Tang YL,Huang LB,Lin WH,et al. Butein inhibits cell proliferation and induces cell cycle arrest in acute lymphoblastic leukemia via FOXO3a/p27kip1 pathway [J]. Oncotarget,2016,7(14):18651-18664.
[17] 江绍钦,李梦强,王玉兵,等.HIF-1α和AMPK在前列腺癌中的表达及临床意义[J].现代泌尿外科杂志,2016, 21(2):104-107.
[18] 熊延路,王明星,卢强,等.AMPK在非小细胞肺癌发生发展中的研究进展[J].现代生物医学进展,2014,14(34):6769-6772.
[19] 崔文贤,许柯青,李元国,等.腺苷酸活化蛋白激酶增强乳腺癌对多柔比星化疗敏感性的机制[J].中国癌症杂志,2016,26(11):908-915.
[20] 易光明,冯艺兰,黄建鸣,等.AMPK在肿瘤放射治疗中的作用[J].肿瘤预防与治疗,2016,29(1):44-48.