[1]习 攀,王 蒨,郭俊俊,等.吉西他滨联合热疗对胰腺癌ASPC-1细胞增殖、迁移、侵袭和凋亡的影响及机制研究[J].陕西医学杂志,2023,52(12):1759-1764.[doi:DOI:10.3969/j.issn.1000-7377.2023.12.029]
　XI Pan,WANG Qian,GUO Junjun,et al.Effects of gemcitabine combined with hyperthermia on proliferation,migration,invasion and apoptosis of pancreatic cancer ASPC-1 cells and its mechanism[J].,2023,52(12):1759-1764.[doi:DOI:10.3969/j.issn.1000-7377.2023.12.029]
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吉西他滨联合热疗对胰腺癌ASPC-1细胞增殖、迁移、侵袭和凋亡的影响及机制研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年12期
页码:
1759-1764
栏目:
临床病理
出版日期:
2023-12-05

文章信息/Info

Title:
Effects of gemcitabine combined with hyperthermia on proliferation,migration,invasion and apoptosis of pancreatic cancer ASPC-1 cells and its mechanism
作者:
习 攀1; 王 蒨1; 郭俊俊1; 李 量1; 李 雅2
(1.陕西省肿瘤医院放疗科,陕西 西安 710061; 2.陕西省肿瘤医院内二科,陕西 西安 710061)
Author(s):
XI Pan; WANG Qian; GUO Junjun; LI Liang; LI Ya
(Department of Radiotherapy,Shaanxi Provincial Cancer Hospital,Xi'an 710061,China)
关键词:
胰腺癌;  热疗;  吉西他滨;  增殖;  迁移;  侵袭;  凋亡
Keywords:
Pancreatic cancer;  Hyperthermia;  Gemcitabine;  Proliferation;  Migration;  Invasion;  Apoptosis
分类号:
R 735.9
DOI:
DOI:10.3969/j.issn.1000-7377.2023.12.029
文献标志码:
A
摘要:
目的:探讨吉西他滨(GEM)联合热疗对胰腺癌ASPC-1细胞增殖、迁移、侵袭和凋亡的影响及可能的机制。方法:将ASPC-1细胞随机分为对照组(无任何处理)、GEM组(给予30 μmol/L GEM)和热化疗组(给予热疗联合30 μmol/L GEM)。采用MTT法检测细胞增殖及活力情况。采用划痕实验和Transwell实验检测细胞迁移和侵袭能力。流式细胞仪检测细胞凋亡情况。采用Westerm blot和实时荧光定量PCR(RT-qPCR)检测特异性蛋白1(Sp1)、细胞周期蛋白D1(Cyclin D1)、环氧合酶-2(COX-2)、B细胞淋巴瘤-2(Bcl-2)蛋白及mRNA表达情况。结果:30 μmol/L GEM对ASPC-1细胞增殖有抑制作用,热化疗组抑制作用更明显(均P<0.05)。GEM前24 h给予43 ℃热疗1 h对细胞抑制作用更明显(均P<0.05)。与对照组比较,GEM组和热化疗组细胞迁移能力降低,且热化疗组降低更加明显(均P<0.05)。GEM组和热化疗组细胞侵袭能力较对照组降低,且热化疗组更明显(均P<0.05)。与对照组比较,GEM组和热化疗组细胞凋亡率升高,且热化疗组高于GEM组(均P<0.05)。与对照组比较,GEM组细胞Sp1、COX-2、Bcl-2蛋白水平降低(均P<0.05)。与GEM组比较,热化疗组Sp1、COX-2蛋白水平降低(均P<0.05)。与对照组比较,GEM组细胞Sp1、COX-2 mRNA表达降低(均P<0.05)。与GEM组比较,热化疗组Sp1、COX-2 mRNA表达降低(均P<0.05)。结论:GEM联合热疗可抑制胰腺癌ASPC-1细胞增殖、迁移和侵袭,并诱导凋亡,其机制可能与抑制Sp1及其下游基因COX-2有关。
Abstract:
Objective:To investigate the effects of gemcitabine(GEM)combined with hyperthermia on the proliferation,migration,invasion and apoptosis of pancreatic cancer ASPC-1 cells and its possible mechanism.Methods:ASPC-1 cells were randomly divided into control group(without any treatment),GEM group(given 30 μmol/L GEM)and thermochemotherapy group(given hyperthermia combined with 30 μmol/L GEM).Cell proliferation and viability were detected by MTT assay.Wound healing assay and Transwell assay were used to detect cell migration and invasion.Apoptosis was assessed by flow cytometry.Western blot and RT-qPCR were used to detect the protein and mRNA expressions of Sp1,Cyclin D1,COX-2,and Bcl-2.Results:GEM(30 μmol/L)inhibited the proliferation of ASPC-1 cells,especially in the thermochemotherapy group(all P<0.05).Hyperthermia at 43 ℃ for 1 hour at 24 hours before GEM had a more significant inhibitory effect on the cells(all P<0.05).Compared with the control group,the cell migration ability was decreased in GEM group and thermochemotherapy group,and the decrease was more obvious in thermochemotherapy group(all P<0.05).The invasive ability of GEM group and thermochemotherapy group was lower than that of the control group,and the thermochemotherapy group was more obvious(all P<0.05).Compared with the control group,the apoptosis rate of GEM group and thermochemotherapy group was increased,and the thermochemotherapy group was higher than GEM group(all P<0.05).Compared with the control group,the protein levels of Sp1,COX-2 and Bcl-2 in the GEM group were decreased(all P<0.05).Compared with the GEM group,the protein levels of Sp1 and COX-2 in the thermochemotherapy group were decreased(all P<0.05).Compared with the control group,the mRNA expression of Sp1 and COX-2 in the GEM group decreased(both P<0.05).Compared with the GEM group,the mRNA expression of Sp1 and COX-2 in the thermochemotherapy group decreased(all P<0.05).Conclusion:GEM combined with hyperthermia can inhibit the proliferation,migration and invasion and induce apoptosis of pancreatic cancer ASPC-1 cells possibly by inhibiting Sp1 and its downstream gene COX-2.

参考文献/References:

[1] Siegel RL,Miller KD,Fuchs HE,et al.Cancer statistics,2021[J].CA Cancer J Clin,2021,71(1):7-33.
[2] Tavakkoli A,Singal AG,Waljee AK,et al.Racial disparities and trends in pancreatic cancer incidence and mortality in the United States[J].Clin Gastroenterol Hepatol,2020,18(1):171-178.
[3] Cronin KA,Lake AJ,Scott S,et al.Annual report to the nation on the status of cancer,part Ⅰ:National cancer statistics[J].Cancer,2018,124(13):2785-2800.
[4] Eheman C,Henley SJ,Ballard BR,et al.Annual report to the nation on the status of cancer,1975-2008,featuring cancers associated with excess weight and lack of sufficient physical activity[J].Cancer,2012,118(3):2338-2366.
[5] Smith BD,Smith GL,Hurri A,et al.Future of cancer incidence in the United States:Burdens upon an aging,changing nation[J].J Clin Oncol,2019,27(5):2758-2765.
[6] Klein AP.Pancreatic cancer epidemiology:Understanding the role of lifestyle and inherited risk factors[J].Nat Rev Gastroenterol Hepatol,2021,18(7):493-502.
[7] Abdel RO.A 10-year review of survival among patients with metastatic gastrointestinal cancers:A population-based study[J].Int J Colorectal Dis,2020,35(5):911-920.
[8] 袁文婷,肖茂良,肖 锋.半枝莲提取物通过PI3K-Akt信号通路抑制胰腺癌模型大鼠肿瘤生长的机制研究[J].陕西中医,2021,42(12):1676-1679.
[9] Siegel R,Naishadham D,Jemal A,et al.Cancer statistics,2013[J].CA Cancer J Clin,2013,63(1):11-30.
[10] Jiang LL,Guo PL,Zhi WX,et al.Cancer statistics:Current diagnosis and treatment of pancreatic cancer in Shanghai,China[J].Cancer Lett,2014,346(2):273-277.
[11] 陈秋霞,杨黎星,马 瑞,等.羧胺三唑乳清酸盐抑制人胰腺癌吉西他滨耐药细胞株增殖及线粒体能量代谢[J].基础医学与临床,2022,42(4):20-23.
[12] 蒋 洁,任加强,王 铮,等.苦参素通过sHH信号通路抑制胰腺癌细胞增殖和侵袭能力研究[J].陕西中医,2021,42(11):1499-1503.
[13] Zhu L,Altman MB,Laszlo A,et al.Ultrasound hyperthermia technology for radiosensitization[J].Ultrasound Med Biol,2019,45(5):1025-1043.
[14] Amichetti C,Graiff G,Fellin G,et al.Cisplatin,hyperthermia,and radiation(trimodal therapy)in patients with locally advanced head and neck tumors:A phase Ⅰ–Ⅱ study[J].Int J Radiat Oncol Biol Phys,1993,26(5):801-807.
[15] 黄凤仙,靳荣辉,高 晖,等.两种不同放疗方案联合热疗治疗骨转移瘤临床研究[J].陕西医学杂志,2021,50(5):550-554.
[16] Jones EL,Oleson JR,Prosnitz LR,et al.Randomized trial of hyperthermia and radiation for superfificial tumors[J].J Clin Oncol,2017,23(13):3079-3085.
[17] Harima Y,Nagata K,Harima K,et al.A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage ⅢB cervical carcinoma[J].Int J Hyperthermia,2020,17(2):97-105.
[18] Zhou Y,Zhong Q,Huang D,et al.The efficacy of adding hyperthermia to the treatment of advanced NSCLC patients based on the states of EGFR[J].Aging,2022,14(12):5223-5232.
[19] Verduijn GM,De-Wee EM,Rijnen Z,et al.Deep hyperthermia with the hypercollar system combined with irradiation for advanced head and neck carcinom:A feasibility study[J].Int J Hyperthermia,2018,34(7):994-1001.
[20] Shi Z,Lan B,Peng B,et al.Combination therapy with BH3 mimetic and hyperthermia tends to be more effective on anti-melanoma treatment[J].Biochem Biophys Res Commun,2018,503(1):249-256.
[21] Kim S,Lee JH,Cha J,et al.Beneficial effects of modulated electro-hyperthermia during neoadjuvant treatment for locally advanced rectal cancer[J].Int J Hyperthermia,2021,38(1):144-151.
[22] Kok HP,Van-Dijk I,Crama KF,et al.Re-irradiation plus hyperthermia for recurrent pediatric sarcoma; a simulation study to investigate feasibility[J].Int J Oncol,2019,54(1):209-218.
[23] Van SR,Albers AJ,Sonke GS,et al.Hyperthermic intraperitoneal chemotherapy for ovarian and colorectal cancer:A review[J].JAMA Oncol,2021,7(8):1231-1238.
[24] Hornor MJ,Rirs LA,Kraocho M,et al.SEER cancer statistics review,1975-2006[J].Cancer,2018,118(6):233-236.
[25] 何申戌,熊六林,于晋生,等.高强度体外聚焦超声治疗腹腔和盆腔恶性肿瘤140例初步报告[J].中华普通外科杂志,2000,15(8):480-482.
[26] 熊六林,赫崇军,姚松森,等.高强度聚焦超声热疗治疗晚期胰腺癌的初步临床应用[J].中华普通外科杂志,2001,16(6):345-347.
[27] 唐亚荣.循环热灌注化疗联合替吉奥及热疗治疗老年胃癌癌性腹水临床研究[J].陕西医学杂志,2019,48(4):435-437.
[28] Wang JH,Wang YN,Waren C,et al.Preclinical in vivo evaluation of an extracorporeal HIFU device for ablation of pancreatic tumors[J].Ultrasound Med Biol,2009,35(6):967-975.
[29] Zuo D,Feng Y,Zhang Q,et al.The value of dynamic contrast enhanced ultrasound(DCE-US)inmonitoring treatment effectof high-intensity focused ultrasound(HIFU)inlocally advanced pancreatic cancer(LAPC)[J].Clin Hemo Microcirc,2021,77(3):323-333.
[30] Xie DR,Chen D,Teng H.A multicenter non-randomized clinical study of high intensity focused ultrasound in treating patients with local advanced pancreatic carcinoma[J].Chin J Clin Oncol,2003,30(2):630-634.
[31] Xiong LL,He CJ,Yao SS,et al.The preliminary clinical results of the treatment for advanced pancreatic carcinoma by high intensity focused ultrasound[J].Chin J Gen Surg,2005,16(3):345-347.
[32] Yuan C,Yang L,Yao C.Observation of high intensity focused ultrasound treating 40 cases of pancreatic cancer[J].Chin J Clin Hep,2003,19(23):145-150.
[33] Zhou Q,Zhu X Q,Zhang J,et al.Changes in circulating immunosuppressive cytokine levels of cancer patients after high intensity focused ultrasound treatment[J].Ultrasound Med Biol,2008,34(1):81-87.
[34] Zhao H,Yang G,Wang D,et al.Concurrent gemcitabine and high-intensity focused ultrasound therapy in patients with locally advanced pancreatic cancer[J].Anticancer Drugs,2010,21(4):447-452.
[35] Hu H,Han T,Zhou M,et al.Elevated COX-2 expression promotes angiogenesis through EGFR/p38-MAPK/Sp1-dependent signaling in pancreatic cancer[J].Sci Rep,2020,26(1):470-475.

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备注/Memo

备注/Memo:
基金项目:陕西省卫生健康科研基金资助项目(2022D046)
更新日期/Last Update: 2023-12-05