芦丁联合奥沙利铂对人胃癌SGC-7901细胞增殖及凋亡的影响

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (10): 1099-1105.

芦丁联合奥沙利铂对人胃癌SGC-7901细胞增殖及凋亡的影响

李琪^1,2，任立群³，王亚帝²，陈素贤²

¹锦州医科大学，²锦州医科大学附属第三医院，锦州 121000，辽宁；³吉林大学药学院，长春 130021，吉林

收稿日期:2017-06-12 修回日期:2017-07-17 出版日期:2017-10-26 发布日期:2017-11-13
通讯作者: 陈素贤，女，博士，副教授，研究方向：胃肠道肿瘤。 Tel：13504060890 E-mail：csxsjpx@163.com
作者简介:李琪，女，在读硕士研究生，研究方向：胃肠道肿瘤。 Tel：18648127612 E-mail：495989040@qq.com
基金资助:
辽宁省自然科学基金项目（2013022007）

Effects of Rutin combined with oxaliplatin on the proliferation and apoptosis of human gastric cancer SGC-7901 Cells

LI Qi^1,2, REN Liqun³, WANG Yadi², CHEN Suxian²

¹Jinzhou Medical University, ² Third Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, Liaoning, China; ³ Jilin University School of Pharmacy, Changchun 130021, Jilin, China

Received:2017-06-12 Revised:2017-07-17 Online:2017-10-26 Published:2017-11-13

摘要/Abstract

摘要：

目的: 探讨芦丁联合奥沙利铂对人胃癌SGC-7901细胞增殖及凋亡的影响。方法:采取对数生长期的人胃癌SGC-7901细胞作为研究对象，应用MTT法检测药物对胃癌SGC-7901细胞生长抑制率；Hoechst33258核染色观察细胞形态学变化；流式细胞术检测细胞周期及细胞凋亡率；Westernblot方法分析SGC-7901细胞中caspase-3、Bax和Bcl-2蛋白表达。结果:芦丁(100、200、300 μmol/L)、奥沙利铂均可抑制SGC-7901的增殖，且呈剂量相关性；芦丁联合奥沙利铂与相同浓度奥沙利铂单用处理SGC-7901细胞相比，前者对SGC-7901细胞的抑制作用更显著(P<0.05)；不同浓度芦丁与奥沙利铂联合处理SGC-7901细胞与奥沙利铂单用相比，前者显著提高了SGC-7901细胞的凋亡率(P<0.05)。芦丁作用后，caspase-3蛋白表达明显升高，Bcl-2/Bax蛋白表达的比值则明显降低(P<0.05)。结论:芦丁和奥沙利铂均可抑制SGC-7901细胞增殖并诱导其凋亡，其机制可能与上调caspase-3、Bax及下调Bcl-2等凋亡相关蛋白表达水平有关；两者联合应用具有一定的协同效应。

关键词: 芦丁, 奥沙利铂, 胃癌, 增殖, 凋亡

Abstract:

AIM: To study the effect of rutin combined with oxaliplatin on the proliferation and apoptosis of human gastric cancer SGC-7901 cells. METHODS: Human gastric cancer SGC-7901 cells in logarithmic growth phase were selected as the research object.Hoechst33258 nuclear staining was used to observe the morphological changes. Cell cycle and cell apoptosis were detected by flow cytometry. The expression of caspase-3, Bax and Bcl-2 protein in SGC-7901 cells were analyzed by Western-blot. RESULTS: Rutin (100,200,300 μmol/L) and oxaliplatin inhibited the proliferation of SGC-7901 in a dose-dependent manner. Rutin combined with oxaliplatin, compared with the same concentration of oxaliplatin SGC-7901 cells, was significantly more effective on SGC-7901 cells (P<0.05). Compared with oxaliplatin, SGC-7901 cells treated with different concentrations of rutin and oxaliplatin significantly increased the apoptosis rate of SGC-7901 cells (P<0.05).The ratio of bcl-2/bax protein expression was significantly decreased (P<0.05). CONCLUSION: Both curcumin and oxaliplatin can inhibit the proliferation of gastric carcer cells SGC-7901 and induce apoptosis. The mechanism may be related to up-regulation of caspase-3 and down-regulation of apoptosis-related protein such as bcl-2/bax. And the joint application of rutin and oxaliplatin presents some synergistic effect.

Key words: rutin, oxaliplatin, gastric cancer, proliferation, apoptosis

中图分类号:

R965.2

李琪，任立群，王亚帝，陈素贤. 芦丁联合奥沙利铂对人胃癌SGC-7901细胞增殖及凋亡的影响[J]. 中国临床药理学与治疗学, 2017, 22(10): 1099-1105.

LI Qi, REN Liqun, WANG Yadi, CHEN Suxian. Effects of Rutin combined with oxaliplatin on the proliferation and apoptosis of human gastric cancer SGC-7901 Cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(10): 1099-1105.

参考文献

［1］邹文斌, 李兆申. 中国胃癌发病率及死亡率研究进展［J］. 中国实用内科杂志, 2014(4):408-415.
［2］Ferlay J, Soerjomataram I, Ervik M, et al. Cancer incidence and mortality worldwide: sources, methods and major pattemas in GLOBOCAN 2012［J］. Int J Cancer, 2015, 136(5):E359-E386
［3］李玉山. 芦丁的资源、药理及主要剂型研究进展［J］. 氨基酸和生物资源, 2013, 35(3): 13-16.
［4］朱葛馨, 王丽霞, 仝小林. 中药安全性研究［J］. 长春中医药大学学报, 2015, 31(1): 32-34.
［5］Alonsocastro AJ, Domínguez F, Garcíacarrancá A. Rutin exerts antitumor effects on nude mice bearing SW480 tumor［J］. Arch Med Res, 2013, 44(5): 346-351.
［6］Li Y, Duan S, Jia H, et al. Flavonoids from tartary buckwheat induce G2/M cell cycle arrest and apoptosis in human hepatoma HepG2 cells ［J］. Acta Biochim Biophys Sin (Shanghai), 2014, 46(6): 460-470.
［7］Karim S, Al-Maghrabi JA, Farsi HMA, et al. Cyclin D1 as a therapeutic target of renal cell carcinoma-a combined transcriptomics, tissue microarray and molecular docking study from the Kingdom of Saudi Arabia［J］. BMC Cancer, 2016, 16(Suppl 2): 741.
［8］Sghaier MB, Pagano A, Mousslim M, et al. Rutin inhibits proliferation, attenuates superoxide production and decreases adhesion and migration of human cancerous cells ［J］. Biomed Pharmacot, 2016, 84: 1972-1978.
［9］Yamauchi K, Mitsunaga T, Batubara I. Synthesis of quercetin glycosides and their melanogenesis stimulatory activity in B16 melanoma cells［J］. Bioorg Med Chem, 2014, 22(3):937-944.
［10］Chen H, Miao Q, Geng M, et al. Anti-tumor effect of rutin on human neuroblastoma cell lines through inducing G2/M cell cycle arrest and promoting apoptosis ［J］. Scientific World Journal, 2013, 2013(11):269165.
［11］Volate SR, Davenport DM, Muga SJ, et al. Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng and rutin) ［J］. Carcinogenesis, 2005, 26(8):1450-1456.
［12］Jessica B, Mathieu D, Ezzeddine B, et al. Hammada scoparia flavonoids and rutin kill adherent and chemoresistant leukemic cells ［J］. Leuk Res, 2011, 35:1093-1101.
［13］Azevedo MI, Pereira AF, Nogueira RB, et al. The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy［J］. Mol Pain, 2013, 9(1): 53.
［14］Li F, Zhang X, Li Y, et al. Phenolics extracted from tartary (Fagopyrum tartaricum L. Gaerth) buckwheat bran exhibit antioxidant activity, and an antiproliferative effect on hum-an breast cancer MDA-MB-231 cells through the p38/MAP kinase pathway［J］. Food Func, 2017, 8(1): 177-188.
［15］Vijay M, Sivagami G, Thayalan K, et al. Radiosensitizing potential of rutin against human col-on adenocarcinoma HT-29 cells［J］. Bratislavské Lekárske Listy, 2016, 117(3)：171-178.

[1]	范杰, 金永明, 江孝龙, 蒋国华. lncRNA HOTAIR调控miR-206影响类风湿关节炎滑膜细胞增殖和凋亡的分子机制研究[J]. 中国临床药理学与治疗学, 2023, 28(7): 736-742.
[2]	王安婧, 王亚亚, 梁轩, 闫雅婕, 苏静, 李彩东. 基于PPAR治疗胆汁淤积性肝病的机制与药物研究进展[J]. 中国临床药理学与治疗学, 2023, 28(7): 796-808.
[3]	杨晓佳, 江萌, 吴敏, 张伊黎, 吕兰, 吴嫄芬, 王鑫昱, 刘立权. 藏红花素介导DKK3调控GSK-3β/β-catenin通路对阿尔兹海默症大鼠的认知改善作用[J]. 中国临床药理学与治疗学, 2023, 28(5): 489-497.
[4]	王艳, 张金辉, 赵永辰, 刘宏祥, 刘亚维, 苗欢欢, 杨信才. 红杉黄酮通过下调PI3K/AKT信号通路抑制胃癌细胞增殖侵袭等干细胞特性[J]. 中国临床药理学与治疗学, 2023, 28(5): 508-513.
[5]	封壮壮, 宋瑞平, 豆鹏程, 陈心怡, 左娇娇, 舒劲. 基于mTOR/Beclin1/LC3信号轴探讨制萎扶胃丸对胃癌前病变大鼠胃窦组织自噬的影响[J]. 中国临床药理学与治疗学, 2023, 28(4): 361-370.
[6]	侯小煜, 冷玉芳, 曹雪芬, 吕兴娇, 韩晓霞, Janvier NIBARUTA, 刘永强. 五味子乙素减轻小鼠肠缺血再灌注损伤的网络药理学分析及实验验证[J]. 中国临床药理学与治疗学, 2023, 28(2): 147-154.
[7]	王丹, 鄢晓丽, 张渊. 幽门螺杆菌感染影响胃癌免疫治疗的研究进展[J]. 中国临床药理学与治疗学, 2023, 28(2): 228-234.
[8]	王剑, 孙永东, 周兴玮, 刘雷, 陈龙, 童兴科, 朱佳丽. 黄芩素经由miR-125b-5p/IRF4轴进而促进喉癌细胞死亡并抑制其侵袭的机制研究[J]. 中国临床药理学与治疗学, 2023, 28(11): 1209-1218.
[9]	朱瑞芳, 郭东凯, 智慧, 江翊国, 张悦翎, 钱晓萍, 季士亮. ROS-NF-κB-p38MAPK通路探索榄香烯联合硼替佐米抗多发性骨髓瘤的机制研究[J]. 中国临床药理学与治疗学, 2023, 28(11): 1219-1226.
[10]	周欢, 徐铭, 李波, 刘春英, 王淳. PI3K/Akt/FOXO3a信号通路介导的保护性自噬参与肺腺癌获得性顺铂耐药表型重塑[J]. 中国临床药理学与治疗学, 2022, 27(9): 961-970.
[11]	华海燕, 严杰, 秦宇芬. 五味子乙素通过抑制心肌细胞凋亡减轻大鼠心肌缺血再灌注损伤的实验研究[J]. 中国临床药理学与治疗学, 2022, 27(8): 848-856.
[12]	丁嘉敏, 王友娣, 赵夏丽, 姜根风, 陈思文, 洪程程, 李书勤, 胡卫华. 生长激素和维生素E联合应用治疗薄型子宫内膜的研究[J]. 中国临床药理学与治疗学, 2022, 27(8): 857-862.
[13]	李雪恒, 李龙. 褪黑素与特发性肺纤维化关系的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(6): 715-720.
[14]	王新丽, 许霞青, 方寒冰, 郭玉忠. 佛波酯增强顺铂的抗肿瘤活性及降低其肾毒性的作用研究[J]. 中国临床药理学与治疗学, 2022, 27(5): 535-543.
[15]	陈佳音, 王丽, 王立军, 童刚领, 马洁, 陈西敬, 卢杨. 有机阳离子转运体基因多态性与奥沙利铂毒性及疗效的相关性研究[J]. 中国临床药理学与治疗学, 2022, 27(2): 171-177.