金雀异黄素对白介素-6诱导下SKOV3人卵巢癌细胞的抑制作用
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摘要
目的探讨不同剂量金雀异黄素对白介素-6(IL-6)诱导的SKOV3人卵巢癌细胞增殖作用及其机制。方法将SKOV3人卵巢癌细胞分为5组,即对照组、IL-6组(25 ng/ml IL-6)、低(25 ng/ml IL-6+80μmol/L金雀异黄素)、中(25 ng/ml IL-6+120μmol/L金雀异黄素)和高剂量金雀异黄素组(25 ng/ml IL-6+160μmol/L金雀异黄素)。然后检测各组细胞增殖抑制率、凋亡率、迁移能力和侵袭能力,Western blot检测细胞CDK4和G1/S-特异性周期蛋白-D1(CyclinD1)表达情况。结果低、中和高剂量金雀异黄素组卵巢癌细胞增殖抑制率明显高于IL-6组(P<0.05),凋亡率明显高于IL-6组(P<0.01),低、中和高剂量金雀异黄素组卵巢癌细胞增殖率随金雀异黄素剂量上升明显降低(P<0.05),而卵巢癌细胞凋亡率随金雀异黄素剂量上升明显增高(P<0.01),上述差异均有统计学意义。低、中和高剂量组金雀异黄素和对照组卵巢癌细胞迁移率和穿膜细胞数明显低于IL-6组,低、中和高剂量金雀异黄素组卵巢癌细胞迁移率和穿膜细胞数随金雀异黄素剂量上升而降低,差异均有统计学意义(P<0.01)。对照组、低、中和高剂量组卵巢癌细胞CDK4和CyclinD1蛋白表达明显低于IL-6组,低、中和高剂量组卵巢癌细胞CDK4和CyclinD1蛋白表达随金雀异黄素剂量上升明显降低,差异均有统计学意义(P<0.01)。结论金雀异黄素可抑制IL-6诱导的SKOV3细胞增殖,其使用剂量越高,抑癌效果越好,机制可能是通过抑制CyclinD1/CDK4信号通路实现。
To investigate the effect and mechanism of genistein with different concentrations on interleukin-6(IL-6)-induced proliferation of human ovarian cancer SKOV3 cells. Methods The SKOV3 cells were divided into control group, IL-6 group(25 ng/ml IL-6) and three genistein treatment groups(25 ng/ml IL-6 combined with 80, 120 and 160 mmol/L genistein phenylacetyl, respectively). The proliferation, apoptosis rate, migration and invasion ability of ovarian cancer cells were evaluated, and the expressions of CDK4 and CyclinD1 protein were detected by Western blot. Result The proliferation inhibition rate of ovarian cancer cells in low, middle and high dose groups was significantly increased than that in IL-6 group(P<0.05), while the apoptosis rate was also significantly increased than that in IL-6 group(P<0.01). The proliferation rate of ovarian cancer cells in low, middle and high dose groups was significantly decreased with the increased concentration of genistein(P<0.05). The migration rate and the number of penetrating cells of ovarian cancer cells in low, middle and high dose groups and control group were significantly decreased than those in IL-6 group(P<0.01). The migration rate and the number of penetrating cells of ovarian cancer cells in low, middle and high dose groups were significantly decreased than those in IL-6 group(P<0.01). The expressions of CDK4 and CyclinD1 protein in ovarian cancer cells of control group, low, medium and high dose groups were significantly decreased than that of IL-6 group(P<0.01). The expressions of CDK4 and CyclinD1 protein in ovarian cancer cells of low, medium and high dose groups were decreased significantly with the increased concentration of genistein(P<0.01). Conclusion Genistein can significantly inhibit the proliferation of SKOV3 cells induced by IL-6. The higher the concentration of genistein, the better inhibition of human ovarian cancer SKOV3 cells. The mechanism may be involved in inhibiting the CyclinD1/CDK4 signaling pathway.
To investigate the effect and mechanism of genistein with different concentrations on interleukin-6(IL-6)-induced proliferation of human ovarian cancer SKOV3 cells. Methods The SKOV3 cells were divided into control group, IL-6 group(25 ng/ml IL-6) and three genistein treatment groups(25 ng/ml IL-6 combined with 80, 120 and 160 mmol/L genistein phenylacetyl, respectively). The proliferation, apoptosis rate, migration and invasion ability of ovarian cancer cells were evaluated, and the expressions of CDK4 and CyclinD1 protein were detected by Western blot. Result The proliferation inhibition rate of ovarian cancer cells in low, middle and high dose groups was significantly increased than that in IL-6 group(P<0.05), while the apoptosis rate was also significantly increased than that in IL-6 group(P<0.01). The proliferation rate of ovarian cancer cells in low, middle and high dose groups was significantly decreased with the increased concentration of genistein(P<0.05). The migration rate and the number of penetrating cells of ovarian cancer cells in low, middle and high dose groups and control group were significantly decreased than those in IL-6 group(P<0.01). The migration rate and the number of penetrating cells of ovarian cancer cells in low, middle and high dose groups were significantly decreased than those in IL-6 group(P<0.01). The expressions of CDK4 and CyclinD1 protein in ovarian cancer cells of control group, low, medium and high dose groups were significantly decreased than that of IL-6 group(P<0.01). The expressions of CDK4 and CyclinD1 protein in ovarian cancer cells of low, medium and high dose groups were decreased significantly with the increased concentration of genistein(P<0.01). Conclusion Genistein can significantly inhibit the proliferation of SKOV3 cells induced by IL-6. The higher the concentration of genistein, the better inhibition of human ovarian cancer SKOV3 cells. The mechanism may be involved in inhibiting the CyclinD1/CDK4 signaling pathway.
引文
[1] 杨念念, 严亚琼, 郑荣寿,等. 中国2009年卵巢癌发病与死亡分析[J]. 中国肿瘤, 2013, 22(8):617-621.
[2] 王丹, 陈晓, 徐葳,等. 自分泌IL-6经Ras/MEK/ERK、PI3K/Akt通路促进卵巢癌细胞黏附和侵袭功能的研究[J]. 免疫学杂志, 2016,32(4):294-298.
[3] 唐甜, 安东建, 曹建国. 癌症中IL-6信号通路研究进展[J]. 现代肿瘤医学, 2016, 24(9):1470-1472.
[4] 盛连兵, 孙凯, 刘海萍, 等. 金雀异黄素调控Egr1/PTEN信号通路诱导卵巢癌SKOV3细胞凋亡的实验研究[J]. 中国妇产科临床杂志, 2017,18(4):341-344.
[5] 陈通克, 陈林华, 王教, 等. MicroRNA-1调控人结肠癌细胞周期及其机制的研究[J]. 中国细胞生物学学报, 2017,39(3):271-279.
[6] 姜婧, 颜宏利, 杜爱英, 等. 金雀异黄素对肝癌Bel-7404细胞放疗增敏作用及其可能的机制[J]. 中国肿瘤生物治疗杂志, 2017, 24(4):395-399.
[7] 唐爱琼, 罗军. 新型金雀异黄素衍生物5-羟基-4’-硝基-7-丙酰氧基异黄酮对人宫颈癌HeLa细胞增殖和凋亡的影响[J]. 肿瘤, 2017, 37(9):924-935.
[8] 赵雅瑮, 孙旸, 黄素辉, 等. IL-6经PI3K/Akt通路诱导卵巢癌细胞对他莫西芬耐药[J]. 中国肿瘤生物治疗杂志, 2017, 24(6):601-607.
[9] 甄井龙, 初晓丽, 丛莎, 等. 金雀异黄素对青年雌性大鼠卵巢组织中雄激素生成关键酶StAR、P450scc、CYP19基因表达的影响[J]. 食品科学, 2018, 39(11):171-176.
[10] 刘磊, 韩亮. 金雀异黄素对胃癌细胞增殖和细胞周期的影响[J]. 中华实验外科杂志, 2015, 32(3):478-480.
[11] Pan H, Fang W, Rankin GO, et al. Inhibitory effect of black tea pigments, theaflavin-3/3′-gallate against cisplatin-resistant ovarian cancer cells by inducing apoptosis and G1 cell cycle arrest[J]. Int J Oncol, 2017, 51(5):1508-1520.
[12] 张爽爽, 夏庆民, 郑荣寿,等. 中国2010年卵巢癌发病与死亡分析[J]. 中国肿瘤, 2016, 25(3):169-173.
[13] 金永生, 刘超美.金雀异黄素的药理作用[J]. 现代药物与临床, 2002, 17(5):190-193.
[14] 徐森, 杨宗元, 靳平, 等. 二甲双胍通过下调IL-6抑制卵巢癌肿瘤相关成纤维细胞活性的研究[J]. 现代妇产科进展, 2016, 25(1):1-5.
[15] 吴晶, 徐加英, 韩淑芬, 等. 金雀异黄素诱导结肠癌HCT-116细胞凋亡及其机制研究[J]. 卫生研究, 2014, 43(1):1-5.
[16] Hoffmann M, Fiedor E, Ptak A. 17?2-estradiol reverses leptin-inducing ovarian cancer cell migration by the PI3K/Akt signaling pathway[J]. Reprod Sci, 2016, 23(11):1600-1608.
[17] Vancurova I, Gatla HR, Vancura A. HDAC/IKK inhibition therapies in solid tumors[J]. Oncotarget, 2017, 8(21):34030-34031.
[18] Wang F, Zhu Y, Fang S, et al. Lanthanum chloride enhances cisplatin-induced apoptosis in ovarian cancer cells[J]. Cell Mol Viol, 2016, 62(7):1-2.
[19] Tiper IV, Temkin SM, Spiegel S, et al. VEGF potentiates GD3-mediated immunosuppression by human ovarian cancer cells[J]. Clin Cancer Res, 2016, 22(16):4249-4258.
[20] Simperova A, Al-Nakkash L, Faust JJ, et al. Genistein supplementation prevents weight gain but promotes oxidative stress and inflammation in the vasculature of female obese ob/ob mice[J]. Nutr Res, 2016, 36(8):789.
[2] 王丹, 陈晓, 徐葳,等. 自分泌IL-6经Ras/MEK/ERK、PI3K/Akt通路促进卵巢癌细胞黏附和侵袭功能的研究[J]. 免疫学杂志, 2016,32(4):294-298.
[3] 唐甜, 安东建, 曹建国. 癌症中IL-6信号通路研究进展[J]. 现代肿瘤医学, 2016, 24(9):1470-1472.
[4] 盛连兵, 孙凯, 刘海萍, 等. 金雀异黄素调控Egr1/PTEN信号通路诱导卵巢癌SKOV3细胞凋亡的实验研究[J]. 中国妇产科临床杂志, 2017,18(4):341-344.
[5] 陈通克, 陈林华, 王教, 等. MicroRNA-1调控人结肠癌细胞周期及其机制的研究[J]. 中国细胞生物学学报, 2017,39(3):271-279.
[6] 姜婧, 颜宏利, 杜爱英, 等. 金雀异黄素对肝癌Bel-7404细胞放疗增敏作用及其可能的机制[J]. 中国肿瘤生物治疗杂志, 2017, 24(4):395-399.
[7] 唐爱琼, 罗军. 新型金雀异黄素衍生物5-羟基-4’-硝基-7-丙酰氧基异黄酮对人宫颈癌HeLa细胞增殖和凋亡的影响[J]. 肿瘤, 2017, 37(9):924-935.
[8] 赵雅瑮, 孙旸, 黄素辉, 等. IL-6经PI3K/Akt通路诱导卵巢癌细胞对他莫西芬耐药[J]. 中国肿瘤生物治疗杂志, 2017, 24(6):601-607.
[9] 甄井龙, 初晓丽, 丛莎, 等. 金雀异黄素对青年雌性大鼠卵巢组织中雄激素生成关键酶StAR、P450scc、CYP19基因表达的影响[J]. 食品科学, 2018, 39(11):171-176.
[10] 刘磊, 韩亮. 金雀异黄素对胃癌细胞增殖和细胞周期的影响[J]. 中华实验外科杂志, 2015, 32(3):478-480.
[11] Pan H, Fang W, Rankin GO, et al. Inhibitory effect of black tea pigments, theaflavin-3/3′-gallate against cisplatin-resistant ovarian cancer cells by inducing apoptosis and G1 cell cycle arrest[J]. Int J Oncol, 2017, 51(5):1508-1520.
[12] 张爽爽, 夏庆民, 郑荣寿,等. 中国2010年卵巢癌发病与死亡分析[J]. 中国肿瘤, 2016, 25(3):169-173.
[13] 金永生, 刘超美.金雀异黄素的药理作用[J]. 现代药物与临床, 2002, 17(5):190-193.
[14] 徐森, 杨宗元, 靳平, 等. 二甲双胍通过下调IL-6抑制卵巢癌肿瘤相关成纤维细胞活性的研究[J]. 现代妇产科进展, 2016, 25(1):1-5.
[15] 吴晶, 徐加英, 韩淑芬, 等. 金雀异黄素诱导结肠癌HCT-116细胞凋亡及其机制研究[J]. 卫生研究, 2014, 43(1):1-5.
[16] Hoffmann M, Fiedor E, Ptak A. 17?2-estradiol reverses leptin-inducing ovarian cancer cell migration by the PI3K/Akt signaling pathway[J]. Reprod Sci, 2016, 23(11):1600-1608.
[17] Vancurova I, Gatla HR, Vancura A. HDAC/IKK inhibition therapies in solid tumors[J]. Oncotarget, 2017, 8(21):34030-34031.
[18] Wang F, Zhu Y, Fang S, et al. Lanthanum chloride enhances cisplatin-induced apoptosis in ovarian cancer cells[J]. Cell Mol Viol, 2016, 62(7):1-2.
[19] Tiper IV, Temkin SM, Spiegel S, et al. VEGF potentiates GD3-mediated immunosuppression by human ovarian cancer cells[J]. Clin Cancer Res, 2016, 22(16):4249-4258.
[20] Simperova A, Al-Nakkash L, Faust JJ, et al. Genistein supplementation prevents weight gain but promotes oxidative stress and inflammation in the vasculature of female obese ob/ob mice[J]. Nutr Res, 2016, 36(8):789.