白蛋白紫杉醇与五氟尿嘧啶联合用药对人胃癌细胞增殖及周期的影响Effects of albumin-bound paclitaxel combined with 5-fluorouracil on proliferation and cycle of gastric cancer cells
成兴真;杨芳;王杨;聂微;刘泽莹;王黔;严芝强;
CHENG Xingzhen;YANG Fang;WANG Yang;NIE Wei;LIU Zeying;WANG Qian;YAN Zhiqiang;Department of Surgery,Guizhou Medical University;Department of Clinical Hematology,School of Medical Laboratory Science,Guizhou Medical University;Center of Clinical Laboratory,the Affiliated Hospital of Guizhou Medical University;Department of Gastrointestinal Surgery,the Affiliated Hospital of Guizhou Medical University;
摘要(Abstract):
目的探索白蛋白紫杉醇(Nab-PTX)与五氟尿嘧啶(5-Fu)联合用药对人胃癌细胞(AGS)增殖及周期的影响。方法对数生长的AGS细胞分为对照组(RMPI 1640, Ctrl组)、Nab-PTX组(Nab-PTX,浓度梯度为0.1、0.2、0.4μmol/L)、5-Fu组(5-Fu,浓度梯度为1、2、4μmol/L)及Nab-PTX+5-Fu组[Nab-PTX+5-Fu,浓度梯度为(0.1+1)、(0.2+2)、(0.4+4)μmol/l];相应药物作用24、48以及72 h,采用CCK-8法检测各组细胞增殖能力,流式细胞术检测细胞周期。结果与Ctrl组相比,Nab-PTX组、5-Fu组、Nab-PTX+5-Fu组细胞增殖能力均受到抑制(P<0.05),且联合用药抑制率较单药明显增加,同时Nab-PTX、5-Fu、Nab-PTX+5-Fu作用于AGS细胞株时抑制率随时间延长而递增;与Ctrl组相比,Nab-PTX组细胞周期阻滞于G2/M期(P<0.05),5-Fu组细胞周期阻滞于S期(P<0.05),Nab-PTX+5-Fu组细胞周期阻滞在S期(P<0.01)。结论 Nab-PTX与5-Fu联合用药较两药单独应用能更有效地抑制细胞增殖,同时也使细胞周期阻滞在S期。
Objective To explore the effect of combined administration of albumin-bound paclitaxel(Nab-PTX) and 5-fluorouracil(5-Fu) on proliferation and cycle of human gastric cancer cells(AGS).Methods AGS at logarithmic growth were divided into control group(RMPI 1640,Ctrl group),Nab-PTX group(Nab-PTX at the concentration gradients of 0.1,0.2,0.4 μmol/L),5-Fu group(5-Fu at the concentration gradients of 1,2,4 μmol/L) and the Nab-PTX+5-Fu group [NabPTX+5-Fu,the concentration gradient is(0.1+1),(0.2+2),(0.4+4) μmol/1].After 24,48,and 72 hours of treatment,CCK-8 assay was used to detect cell proliferation in each group,and flow cytometry was used to detect cell cycle.Results Compared with the Ctrl group,the cell proliferation was inhibited in Nab-PTX,5-Fu group and Nab-PTX+5-Fu groups(P <0.05).The inhibition rate was significantly increased in Nab-PTX+5-Fu group when compared with individual drugs.At the same time,the inhibition rates in Nab-PTX,5-Fu,and Nab-PTX+5-Fu were time-dependent.Compared with the Ctrl group,Nab-PTX group was arrested at G2/M phase(P <0.05),5-Fu group at in S phase(P <0.05) and Nab-PTX+5-Fu group at S phase(P <0.01).Conclusion The combination of Nab-PTX and 5-Fu can inhibit cell proliferation more effectively than the two drugs alone and block the cell cycle in S phase.
关键词(KeyWords):
胃癌细胞;白蛋白紫杉醇;五氟尿嘧啶;细胞增殖;细胞周期;联合用药
gastric cancer cells;albumin-bound paclitaxel(Nab-PTX);5-fluorouracil(5-Fu);cell proliferation;cell cycle;drug combination
基金项目(Foundation): 贵州省科技计划项目学术新苗(19NSP015)
作者(Authors):
成兴真;杨芳;王杨;聂微;刘泽莹;王黔;严芝强;
CHENG Xingzhen;YANG Fang;WANG Yang;NIE Wei;LIU Zeying;WANG Qian;YAN Zhiqiang;Department of Surgery,Guizhou Medical University;Department of Clinical Hematology,School of Medical Laboratory Science,Guizhou Medical University;Center of Clinical Laboratory,the Affiliated Hospital of Guizhou Medical University;Department of Gastrointestinal Surgery,the Affiliated Hospital of Guizhou Medical University;
DOI: 10.19367/j.cnki.2096-8388.2021.11.008
参考文献(References):
- [1] SHARMA S, GANESH T, KINGSTON D G, et al. Promotion of tubulin assembly by poorly soluble taxol analogs[J]. Analytical Biochemistry, 2007, 360(1):56-62.
- [2] STEINMETZ M O, PROTA A E. Microtubule-targeting agents:strategies to hijack the cytoskeleton[J]. Trends in Cell Biology, 2018, 28(10):776-792.
- [3]日本胃癌学会.胃癌治療ガイドライン[S]. 5版.東京:金原出版株式会社,2018.
- [4] WATSON S, DE LA FOUCHARDIèRE C, KIM S, et al.Oxaliplatin, 5-Fluorouracil and Nab-paclitaxel as perioperative regimen in patients with resectable gastric adenocarcinoma:a GERCOR phase II study(FOXAGAST)[J]. European Journal of Cancer(Oxford, England:1990), 2019, 107:46-52.
- [5] BANDO H, SHIMODAIRA H, FUJITANI K, et al. A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer[J]. European Journal of Cancer(Oxford,England:1990), 2018, 91:86-91.
- [6] TAKASHIMA A, SHITARA K, FUJITANI K, et al. Peritoneal metastasis as a predictive factor for nab-paclitaxel in patients with pretreated advanced gastric cancer:an exploratory analysis of the phase III ABSOLUTE trial[J].Gastric Cancer:Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2019, 22(1):155-163.
- [7] NAKAYAMA N, ISHIDO K, CHIN K, et al. A phase I study of S-1 in combination with nab-paclitaxel in patients with unresectable or recurrent gastric cancer[J]. Gastric Cancer, 2017, 20(2):350-357.
- [8]唐程,王妍,于珊,等.白蛋白结合型紫杉醇联合替吉奥治疗胃癌腹膜转移的疗效分析[J].中国临床医学,2020, 27(6):983-987.
- [9]高爽,胡长路.阿帕替尼联合白蛋白结合型紫杉醇治疗老年复发转移性胃癌的疗效及安全性评价[J].国际肿瘤学杂志,2020, 47(11):669-674.
- [10]毕志彬.白蛋白紫杉醇联合奥沙利铂氟尿嘧啶在胃癌转化治疗中的疗效分析[J].中国药物与临床,2020,20(20):3435-3437.
- [11]司海燕,苟苗苗,赵海清,等.白蛋白结合型紫杉醇用于HER2阴性晚期胃癌一线化疗中的疗效分析[J].解放军医学院学报,2020, 41(10):976-982.
- [12]方科,张战民.白蛋白结合型紫杉醇联合替吉奥一线治疗晚期胃癌的回顾性分析[J].中国医学创新,2020, 17(7):40-44.
- [13]龚继芳,李洁,李燕,等.纳米白蛋白结合型紫杉醇联合替吉奥胶囊二线治疗进展期胃癌的效果[J].肿瘤综合治疗电子杂志,2018, 4(1):48-53.
- [14]中国临床肿瘤学会指南工作委员会.中国临床肿瘤学会(CSCO)胃癌治疗指南2020[S].北京:人民卫生出版社,2020.
- [15]AJANI J A, D'AMICO TA, BENTREM D J, et al. Gastric cancer, version 4. 2021, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw.2021,10(8):1186-1232.
- [16]KERIN M J. Cancer principles and practice of oncology[J]. Surgical Oncology, 1997, 6(2):125.
- [17]YU B Q, XIE J W. Identifying therapeutic targets in gastric cancer:the current status and future direction[J].Acta Biochimica et Biophysica Sinica, 2016, 48(1):90-96.
- [18]HE M M, WANG F, JIN Y, et al. Phase II clinical trial of S-1 plus nanoparticle albumin-bound paclitaxel in untreated patients with metastatic gastric cancer[J]. Cancer Science, 2018, 109(11):3575-3582.
- [19] SHITARA K, TAKASHIMA A, FUJITANI K, et al.Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer(ABSOLUTE):an open-label, randomised, non-inferiority,phase 3 trial[J]. The Lancet Gastroenterology&Hepatology, 2017, 2(4):277-287.
- [20]IBRAHIM N K, DESAI N, LEGHA S, et al. Phase I and pharmacokinetic study of ABI-007, a Cremophorfree, protein-stabilized, nanoparticle formulation of paclitaxel[J]. Clinical Cancer Research, 2002, 8(5):1038-1044.
- [21] YARDLEY D A. Nab-Paclitaxel mechanisms of action and delivery[J]. Journal of Controlled Release, 2013,170(3):365-372.
- [22]XIAO X, CHEN W, WEI Z W, et al. The anti-tumor effect of nab-paclitaxel proven by patient-derived organoids[J]. Onco Targets and Therapy, 2020, 13:6017-6025.
- [23] PASSACANTILLI I, PANZERI V, TERRACCIANO F,et al. Co-treatment with gemcitabine and nab-paclitaxel exerts additive effects on pancreatic cancer cell death[J]. Oncology Reports, 2018, 39(4):1984-1990.
- [24] MORGAN D O. Cyclin-dependent kinases:engines,clocks, and microprocessors[J]. Annual Review of Cell and Developmental Biology, 1997, 13:261-291.
- [25]BERTOLI C, SKOTHEIM J M, DE BRUIN R A M. Control of cell cycle transcription during G1 and S phases[J]. Nature Reviews Molecular Cell Biology, 2013, 14(8):518-528.
- [26]TOPACIO B R, ZATULOVSKIY E, CRISTEA S, et al.Cyclin D-Cdk4, 6 drives cell-cycle progression via the retinoblastoma protein's C-terminal helix[J]. Molecular Cell, 2019, 74(4):758-770.
- [27]CAO X, HOU J Y, AN Q L, et al. Towards the overcoming of anticancer drug resistance mediated by p53 mutations[J]. Drug Resistance Updates, 2020, 49:100671.
文章评论(Comment):
|
||||||||||||||||||
|
- 胃癌细胞
- 白蛋白紫杉醇
- 五氟尿嘧啶
- 细胞增殖
- 细胞周期
- 联合用药
gastric cancer cells - albumin-bound paclitaxel(Nab-PTX)
- 5-fluorouracil(5-Fu)
- cell proliferation
- cell cycle
- drug combination
- 成兴真
- 杨芳
- 王杨
- 聂微
- 刘泽莹
- 王黔
- 严芝强
CHENG Xingzhen- YANG Fang
- WANG Yang
- NIE Wei
- LIU Zeying
- WANG Qian
- YAN Zhiqiang
- Department of Surgery
- Guizhou Medical University
- Department of Clinical Hematology
- School of Medical Laboratory Science
- Guizhou Medical University
- Center of Clinical Laboratory
- the Affiliated Hospital of Guizhou Medical University
- Department of Gastrointestinal Surgery
- the Affiliated Hospital of Guizhou Medical University
- 成兴真
- 杨芳
- 王杨
- 聂微
- 刘泽莹
- 王黔
- 严芝强
CHENG Xingzhen- YANG Fang
- WANG Yang
- NIE Wei
- LIU Zeying
- WANG Qian
- YAN Zhiqiang
- Department of Surgery
- Guizhou Medical University
- Department of Clinical Hematology
- School of Medical Laboratory Science
- Guizhou Medical University
- Center of Clinical Laboratory
- the Affiliated Hospital of Guizhou Medical University
- Department of Gastrointestinal Surgery
- the Affiliated Hospital of Guizhou Medical University