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- 2018
2-丁亚砜-1,4-萘醌诱导人恶性黑色素瘤A375细胞凋亡及其机制
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Abstract:
摘要 目的:探究2-丁亚砜-1,4-萘醌(BSNQ)对人恶性黑色素瘤A375细胞的诱导凋亡作用,阐明其诱导凋亡的机制.方法:MTT比色法检测BSNQ对人黑色素瘤A375细胞的杀伤作用.Annexin V-FITC/PI双染法与流式细胞术检测BSNQ对人黑色素瘤A375细胞的诱导凋亡作用.Western blotting法检测Akt信号通路相关蛋白的表达情况.流式细胞术检测BSNQ对A375细胞内ROS的调控作用.结果:BSNQ处理A375细胞其存活率逐渐降低.BSNQ能够显著诱导A375细胞发生凋亡.抗凋亡蛋白p-Akt和Bcl-2表达量逐渐降低,pro-caspase-3表达量逐渐降低,促凋亡蛋白Bad和cleaved-caspase-3表达量逐渐升高(P<0.05).BSNQ能够显著增加细胞内ROS水平.同时,BSNQ与NAC共同处理后,能够显著降低BSNQ诱导的细胞凋亡程度.结论:BSNQ通过上调细胞内ROS水平,下调Akt信号通路的活性,诱导人黑色素瘤A375细胞凋亡.
| [1] | TANG Z, YI F, GUO D M, et al.The regulation of apoptosis on aging and the research progress of in tumor development and treatment[J]. Journal of Jinan University (Natural Science & Medicine Edition), 2016, 37(3): 215-220. |
| [2] | 管鹏健, 徐德锋, 李绍顺. 萘醌类化合物抗肿瘤活性研究进展[J]. 中国药物化学杂志, 2004, 14(4): 249-256. |
| [3] | LIU C, LUO Y H, JIANG X Y, et al.Effect of emodin on inhibiting proliferation and inducing apoptosis in human hepatoma Huh7 cells and its mechanisms[J]. Drug Evaluation Research, 2016, 39(3): 367-371. |
| [4] | SHI T T, BAI J P, LIANG Y Q, et al.Effect of apigenin on the cardiomyocyte apoptosis in rats with ischemia and reperfusion and the expression of Bcl-2, Bax, Caspase-3[J]. Chinese Pharmacological Bulletin, 2011, 27(5): 666-671. |
| [5] | LUO Y H, LIU C, SUN H N, et al.Effect of emodin on proliferation and apoptosis of human lung cancer A549 cells and its mechanism[J]. Journal of Heilongjiang Bayi Agricultural University, 2017, 29(2): 64-67. |
| [6] | JIANG X Y, PIAO X J, LIU C, et al.Apoptotic effect of 4, 5, 6, 7-tetrabromobenzotriazole on human cervical cancer HeLa cells and its mechanism[J]. Journal of Jilin University (Medicine Edition), 2017, 43(3): 561-565. |
| [7] | CRUZ C M, RINNA A, FORMAN H J, et al.ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages[J]. J Biol Chem, 2007, 282(5): 2871-2879. |
| [8] | LI X J, LI Z F, LI X P, et al.In vitro effects of tanshinone ⅡA on autophagy of A375 melanoma cells and related signaling pathway[J]. Chinese Journal of Dermatology, 2017, 50(1): 29-32. |
| [9] | FANG F, ZHAO L Z, LI Q, et al.Cell cycle effect of Juglone on ovarian cancer SKOV3 cell[J]. Lishizhen Medicine and Materia Medica Research, 2015, 26(11): 2575-2577. |
| [10] | LI Y C, HE S M, HE Z X, et al.Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells[J]. Cancer Letters, 2014, 344(2): 239-259. |
| [11] | HAFEEZ B B, JAMAL M S, FISCHER J W, et al.Plumbagin, a plant derived natural agent inhibits the growth of pancreatic cancer cells in vitro and in vivo via targeting EGFR, Stat3 and NF-kB signaling pathways[J]. International Journal of Cancer, 2012, 131(9): 2175-2186. |
| [12] | 李小静, 李志锋, 李显平, 等. 丹参酮ⅡA体外促进黑素瘤A375细胞自噬及信号通路的实验研究[J]. 中华皮肤科杂志, 2017, 50(1): 29-32. |
| [13] | 田红, 肖桂芝, 田苗, 等. 黑色素瘤治疗药物的研究进展[J]. 现代化合物与临床, 2015, 30(7): 890-896. |
| [14] | TIAN H, XIAO G Z, TIAN M, et al.Analysis on current situation and development trend of melanoma drugs[J]. Drugs & Clinic, 2015, 30(7): 890-896. |
| [15] | EGGERMONT A M, SPATZ A, ROBERT C.Cutaneous melanoma[J]. Lancet, 2014, 383(9919): 816-827. |
| [16] | 林子存, 丁孺孺, 张鹏. 1, 4-萘醌及其衍生物的药理作用研究进展[J]. 医药卫生全文版, 2017, 3(1): 285. |
| [17] | LIN Z C, DING R R, ZHANG P.Research progress on pharmacological activities of 1, 4-Naphthoquinone and its Derivatives[J]. Yi Yao Wei Sheng, 2017, 3(1): 285. |
| [18] | 方芳, 赵良中, 李强, 等. 胡桃醌对卵巢癌SKOV3细胞周期影响[J]. 时珍国医国药, 2015, 26(11): 2575-2577. |
| [19] | LEE K, CHO S H, LEE J H, et al.Synthesis of a novel series of 2-alkylthio substituted naphthoquinones as potent acyl-CoA: Cholesterol acyltransferase (ACAT) inhibitors[J]. European Journal of Medicinal Chemistry, 2013, 62(7): 515-525. |
| [20] | 蒋雪园, 朴仙姬, 刘畅, 等. 四溴苯三唑对宫颈癌HeLa细胞凋亡的诱导作用及其机制[J]. 吉林大学学报(医学版), 2017, 43(3): 561-565. |
| [21] | 李朋军, 沈伟哉, 叶文才, 等. 右旋一叶萩碱对小鼠黑色素瘤B16增殖及细胞周期的影响[J]. 暨南大学学报(自然科学与医学版), 2011, 32(2): 151-154. |
| [22] | LI P J, SHEN W Z, YE W C, et al.Effect of virosecurinine on proliferation and cell cycle of mouse melanoma cell line B16[J]. Journal of Jinan University (Natural Science & Medicine Edition), 2011, 32(2): 151-154. |
| [23] | 唐珍, 易芳, 郭冬梅, 等. 细胞凋亡对衰老的调节在肿瘤的发生发展及治疗的研究进展[J]. 暨南大学学报(自然科学与医学版), 2016, 37(3): 215-220. |
| [24] | GUAN P J, XU D F, LI Z S.Advances in the antitumor activitis of naphthoquinones[J]. Chinese Journal of Medicinal Chemistry, 2004, 14(4): 249-256. |
| [25] | 王汝兴, 鲁艳杰, 周健. 紫草素对人卵巢癌细胞SKOV3细胞增殖和凋亡的影响[J]. 中药药理与临床, 2016, 23(2): 76-79. |
| [26] | WANG R X, LU Y J, ZHOU J.Effects of shikonin on cellproliferation and apoptosis of human ovarian cancer cellline SKOV3[J]. Pharmacology and Clinics of Chinese Materia Medica, 2016, 32(2): 76-79. |
| [27] | 陈家劲, 王娟娟, 张鹏, 等. 重楼活性单体PP-26抑制结肠癌SW620细胞增殖并诱导细胞凋亡[J]. 暨南大学学报(自然科学与医学版), 2015, 36(2): 30-36. |
| [28] | CHEN J J, WANG J J, ZHANG P, et al.A monomer purified from Paris Polyphylla, PP-26 inhibits cell growth and induces apoptosis of human colorectal cancer SW620 cells[J]. Journal of Jinan University(Natural Science & Medicine Edition), 2015, 36(2): 30-36. |
| [29] | 孟令旗, 刘畅, 孙虎男, 等. 醌茜素对人肺癌A549细胞增殖、凋亡的影响及初步机制研究[J]. 中国药理学通报, 2016, 32(11): 1625-1626. |
| [30] | MENG L Q, LIU C, SUN H N, et al.Effects of quinalizarin on proliferation and apoptosis of human lung cancer A549 cells and its possible mechanism[J]. Chinese Pharmacological Bulletin, 2016, 32(11): 1625-1626. |
| [31] | VELASCO G, SáNCHEZ C, GUZMáN M. Anticancer mechanisms of cannabinoids[J]. Curr Oncol, 2016, 23(2): S23-32. |
| [32] | ZHANG G, WANG C, SUN M, et al.Cinobufagin inhibits tumor growth by inducing intrinsic apoptosis through AKT signaling pathway in human nonsmall cell lung cancer cells[J]. Oncotarget, 2016, 7(20): 28935-28946. |
| [33] | 刘畅, 罗英花, 蒋雪园, 等. 大黄素对人肝癌Huh7细胞的凋亡作用及机制研究[J]. 药物评价研究, 2016, 39(3): 367-371. |
| [34] | 史婷婷, 白建平, 梁月琴, 等. 芹菜素对大鼠缺血/再灌注心肌细胞凋亡及相关蛋白Bcl-2, Bax, Casepase-3表达的影响[J]. 中国药理学通报, 2011, 27(5): 666-671. |
| [35] | 罗英花, 刘畅, 孙虎男, 等. 大黄素对人肺癌A549细胞增殖、凋亡的影响及机制探讨[J]. 黑龙江八一农垦大学学报, 2017, 29(2): 64-67. |
| [36] | FLEURY C, MIGNOTTE B, VAYSSIERE J L.Mitochondrial reactive oxygen species in cell death signaling[J]. Biochimie, 2002, 84(2/3): 131-141. |
