[1]习 攀,王 蒨,郭俊俊,等.吉西他滨联合热疗对胰腺癌PANC-1细胞凋亡的影响及机制研究[J].陕西医学杂志,2023,52(9):1130-1134.[doi:DOI:10.3969/j.issn.1000-7377.2023.09.004]
 XI Pan,WANG Qian,GUO Junjun,et al.Effect and mechanism of gemcitabine combined with hyperthermia on apoptosis of pancreatic cancer PANC-1 cells[J].,2023,52(9):1130-1134.[doi:DOI:10.3969/j.issn.1000-7377.2023.09.004]
点击复制

吉西他滨联合热疗对胰腺癌PANC-1细胞凋亡的影响及机制研究
分享到:

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年9期
页码:
1130-1134
栏目:
基础研究
出版日期:
2023-09-05

文章信息/Info

Title:
Effect and mechanism of gemcitabine combined with hyperthermia on apoptosis of pancreatic cancer PANC-1 cells
作者:
习 攀1王 蒨1郭俊俊1李 量1张 璞2
(1.陕西省肿瘤医院放疗科,陕西 西安 710061; 2.陕西省核工业二一五医院胸外科,陕西 咸阳 712000)
Author(s):
XI PanWANG QianGUO JunjunLI LiangZHANG Pu
(Department of Radiotherapy,Shaanxi Provincial Cancer Hospital,Xi'an 710061,China)
关键词:
胰腺癌 热疗 吉西他滨 细胞凋亡 活性氧 特异性蛋白1
Keywords:
Pancreatic cancer Hyperthermia Gemcitabine Apoptosis Reactive oxygen species Specifieity protein 1
分类号:
R 735.9
DOI:
DOI:10.3969/j.issn.1000-7377.2023.09.004
文献标志码:
A
摘要:
目的:探索吉西他滨(GEM)联合热疗对胰腺癌PANC-1细胞凋亡的影响及机制。方法:将人胰腺癌PANC-1细胞随机分为对照组(无任何处理)、GEM组(给予GEM)和热化疗组(给予热疗联合GEM)。比较各组细胞增殖、凋亡、活性氧(ROS)、特异性蛋白1(Sp1)及其下游蛋白表达情况。评估ROS抑制剂N-乙酰半胱氨酸(NAC)对各组细胞增殖及相关蛋白表达的影响。结果:GEM对PANC-1细胞增殖的抑制作用呈剂量和时间依赖性。30 μmol/L GEM对PANC-1细胞增殖的抑制作用高于其他剂量(均P<0.05)。在GEM治疗前热疗1 h细胞存活率显著低于GEM与热疗同时1 h和GEM治疗后热疗1 h(均P<0.05)。与对照组比较,GEM组和热化疗组细胞凋亡率增加,且热化疗组高于GEM组(均P<0.05)。与对照组比较,GEM组和热化疗组ROS升高,且热化疗组高于GEM组(均P<0.05)。与对照组比较,GEM组和热化疗组Sp1、B细胞淋巴瘤-2(Bcl-2)蛋白表达水平降低,且热化疗组低于GEM组(均P<0.05)。与GEM组比较,热化疗组环氧合酶-2(Cox-2)蛋白表达水平降低(P<0.05)。加入NAC后热化疗组细胞存活率较加入前升高,30 μmol/L NAC对PANC-1细胞增殖的影响更显著(均P<0.05)。30 μmol/L NAC显著恢复了Sp1及其下游Cox-2和Bcl-2蛋白的表达(均P<0.05)。结论:GEM联合热疗通过诱导ROS的产生抑制胰腺癌PANC-1细胞增殖,促进细胞凋亡,进而抑制Sp1及其下游相关蛋白的表达。
Abstract:
Objective:To explore the effect and mechanism of gemcitabine(GEM)combined with hyperthermia on apoptosis of pancreatic cancer PANC-1 cells.Methods:Human pancreatic cancer PANC-1 cells were randomly divided into control group(without any treatment),GEM group(treated with GEM)and thermochemotherapy group(treated with hyperthermia combined with GEM). Cell proliferation,apoptosis,reactive oxygen species(ROS),specific protein 1(Sp1)and its downstream protein expression were compared among the groups.The effects of ROS inhibitor N-acetylcysteine(NAC)on cell proliferation and related protein expression were evaluated.Results: GEM inhibited the proliferation of PANC-1 cells in a dose- and time-dependent manner.The inhibitory effect of 30 μmol/L GEM on the proliferation of PANC-1 cells was higher than that of other doses(all P<0.05).The cell survival rate of hyperthermia for 1 hour before GEM treatment was significantly lower than that of both GEM and hyperthermia for 1 hour and that of hyperthermia for 1 hour after GEM treatment(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,ROS level was increased in the GEM group and the thermochemotherapy group,and the thermochemotherapy group was higher than GEM group(all P<0.05).Compared with the control group,the protein expression levels of Sp1 and Bcl-2 in the GEM group and the thermochemotherapy group were decreased,and the thermochemotherapy group was lower than GEM group(all P<0.05).Compared with the GEM group,the expression of cyclooxygenase-2(Cox-2)protein was decreased in the thermochemotherapy group(P<0.05).After the addition of NAC,the survival rate of PANC-1 cells in the thermochemotherapy group was higher than that before the addition of NAC,and the effect of 30 μmol/L NAC on the proliferation of PANC-1 cells was more significant(all P<0.05).30 μmol/L NAC significantly restored the protein expressions of Sp1 and its downstream Cox-2 and Bcl-2(all P<0.05).Conclusion:GEM combined with hyperthermia inhibits the proliferation and promotes apoptosis of PANC-1 cells by inducing the production of ROS,thereby inhibiting the expression of Sp1 and its downstream proteins.

参考文献/References:

[1] Rahib L,Wehner MR,Matrisian LM,et al.Estimated projection of us cancer incidence and death to 2040[J].JAMA Netw Open,2021,4(4):e214708.
[2] Zhang L,Sanagapalli S,Stoita A,et al.Challenges in diagnosis of pancreatic cancer[J].World J Gastroenterol,2018,24(19):2047-2060.
[3] 王 旭,程 合,刘 辰,等.2022年度胰腺癌研究及诊疗新进展[J].中国癌症杂志,2023,33(1):1-13.
[4] 陈 娟,朱凤婷,冯冬婵,等.清胰化积汤联合介入化疗栓塞治疗晚期胰腺癌临床研究[J].陕西中医,2023,44(2):178-182.
[5] 杨尹默,田孝东,许静涌,等.胰腺癌临床研究回顾与展望[J].中国实用外科杂志,2020,40(1):48-52.
[6] 安革利,董 峰,宋利芳.胰腺癌根治术后患者预后的相关影响因素[J].实用癌症杂志,2023,38(1):126-128.
[7] 王延磊,王政华.CT引导下125I粒子植入联合吉西他滨、卡培他滨治疗局部进展期胰腺癌临床疗效观察[J].陕西医学杂志,2020,49(12):1604-1607.
[8] Mncguiga A,Kelly P,Turkington RC,et al.Pancreatic cancer:A review of clinical diagnosis,epidemiology,treatment and outcomes[J].World J Gastroenterol,2018,24(43):4846-4861.
[9] 刘 亮,王文权,楼文晖.胰腺癌综合治疗——从理论基础到临床实践[J].中国实用外科杂志,2022,42(5):498-502.
[10] 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.
[11] 央 茂,冯佳毅,刘颖斌,等.胰腺癌化疗中吉西他滨耐药机制研究进展[J].中国实用外科杂志2022,42(2):225-229.
[12] 张思楠,张丽娜.吉西他滨在胰腺癌治疗中的研究进展[J].广东化工,2022,49(16):86-87.
[13] Iyikesici MS.Long-term survival outcomes of metabolically supported chemotherapy with gemcitabine-based or FOLFIRINOX regimen combined with ketogenic diet,hyperthermia,and hyperbaric oxygen therapy in metastatic pancreatic cancer[J].Complement Med Res,2020,27(1):31-39.
[14] He M,Sun J,Zhao D,et al.Modified-FOLFIRINOX combined with deep regional hyperthermia in pancreatic cancer:A retrospective study in Chinese patients[J].Int J Hyperthermia,2019,36(1):394-402.
[15] Fiorentini G,Sarti D,Casadeiv C,et al.Modulated electro-hyperthermia as palliative treatment for pancreatic cancer:A retrospective observational study on 106 patients[J].Integr Cancer Ther,2019,18(3):20-28.
[16] 燕 婧,冯 芸,李 丹,等.microRNA-185-5p真核表达载体构建及其对胰腺癌Panc-1细胞增殖的影响[J].陕西医学杂志,2021,50(11):1323-1326.
[17] Ba MC,Long H,Wang S,et al.Hyperthermia enhances radiosensitivity of colorectal cancer cells through ROS inducing autophagic cell death[J].J Cell Biochem,2018,119(4):3763-3774.
[18] Shimomura O,Oda T,Hashimoto M,et al.Survival impact on triple-modal strategy comprising hyperthermia,external radiation,and chemotherapy for unresectable locally advanced(UR-LA)pancreatic ductal adenocarcinoma[J].Surg Oncol,2021,37(5):101-108.
[19] 范 蕾,齐 青,王文玲,等.调强放疗联合热疗治疗晚期胰腺癌的临床观察[J].肿瘤药学,2020,10(6):714-718.
[20] 岳文宇,王凌霄,霍忠超.微波热疗联合调强放疗治疗晚期胰腺癌临床研究[J].吉林医药学院学报,2021,42(6):409-411.
[21] 王超超,余伟明,梁家乐,等.化疗联合热疗治疗中晚期胰腺癌疗效Meta分析[J].华北理工大学学报:医学版,2022,24(6):467-474.
[22] 李雅哲,张 阳,孙婧华.深部热疗对胰腺癌免疫功能影响的研究进展[J].大连医科大学学报,2019,41(2):175-178.
[23] Jin H,Zhao Y,Yang J,et al.Hyperthermia enhances the sensitivity of pancreatic cancer SW1990 cells to gemcitabine through ROS/JNK signaling[J].Oncol Lett,2018,16(5):6742-6748.
[24] Safe S,Abbruzzese J,Abdelrahim M,et al.Specificity protein transcription factors and cancer:Opportunities for drug development[J].Cancer Prev Res(Phila),2018,11(7):371-382.
[25] Yang J,Wang J,Zhang H,et al.Transcription factor Sp1 is upregulated by pkciota to drive the expression of YAP1 during pancreatic carcinogenesis[J].Carcinogenesis,2021,42(3):344-356.
[26] 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,2018,7(1):470-475.

相似文献/References:

[1]宋亚邛,胡海燕△.VEGF、TGF-β1、CA19-9、CA242和DKK1联合检测对早期胰腺癌临床诊断价值研究*[J].陕西医学杂志,2020,49(2):237.
 SONG Yaqiong,HU Haiyan..Clinical value analysis of combined examination of VEGF,TGF-β1,CA19-9,CA242 and DKK1 in patients with early pancreatic cancer[J].,2020,49(9):237.
[2]王延磊,王政华△.CT引导下125I粒子植入联合吉西他滨、卡培他滨治疗局部进展期胰腺癌临床疗效观察*[J].陕西医学杂志,2020,49(12):1604.[doi:DOI:10.3969/j.issn.1000-7377.2020.12.017]
 WANG Yanlei,WANG Zhenghua..Clinical efficacy of CT-guided 125I particle implantation combined with gemcitabine and capecitabine in treatment of locally advanced pancreatic cancer[J].,2020,49(9):1604.[doi:DOI:10.3969/j.issn.1000-7377.2020.12.017]
[3]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.[doi:DOI:10.3969/j.issn.1000-7377.2021.05.009]
 HUANG Fengxian,JIN Ronghui,GAO Hui,et al.Clinical efficacy of two different radiotherapy regimens combined with hyperthermia in treatment of bone metastases[J].,2021,50(9):550.[doi:DOI:10.3969/j.issn.1000-7377.2021.05.009]
[4]依力哈木·买买提,钟 锴,艾合散·卡马力,等.环状RNA circ_0020123靶向调控微小RNA-145影响胰腺癌细胞SW-1990增殖、侵袭与转移实验研究[J].陕西医学杂志,2023,52(9):1140.[doi:DOI:10.3969/j.issn.1000-7377.2023.09.006]
 YILIHAMU Maimaiti,ZHONG Kai,AIHESAN Kamali,et al.Circular RNA circ_0020123 affects proliferation,invasion and metastasis of pancreatic cancer cell SW-1990 by targeting microRNA-145[J].,2023,52(9):1140.[doi:DOI:10.3969/j.issn.1000-7377.2023.09.006]
[5]周聪雅,金 龙,张 苏,等.糖脂代谢与胰腺癌患者预后相关性分析[J].陕西医学杂志,2023,52(9):1218.[doi:DOI:10.3969/j.issn.1000-7377.2023.09.024]
[6]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.[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(9):1759.[doi:DOI:10.3969/j.issn.1000-7377.2023.12.029]

备注/Memo

备注/Memo:
基金项目:陕西省卫生健康委员会科研基金资助项目(2022D046)
更新日期/Last Update: 2023-09-04