环氧化酶-2反义RNA联合塞莱昔布对肝癌细胞增殖和凋亡的影响

朱跃坤; 赵宪琪; 汪大伟; 张伟; 田茂霖; 李正天; 赵龙; 李超; 姜洪池

doi:10.3969/j.issn.1001-5256.2018.12.021

环氧化酶-2反义RNA联合塞莱昔布对肝癌细胞增殖和凋亡的影响

DOI: 10.3969/j.issn.1001-5256.2018.12.021

哈尔滨医科大学附属第一医院普外科

基金项目:

黑龙江省青年科学基金(QC2009C17)；黑龙江省教育厅科学技术研究基金(11541201)；

详细信息

中图分类号: R735.7
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出版历程
- 出版日期: 2018-12-20

Effect of cyclooxygenase-2 antisense RNA combined with celecoxib on the proliferation and apoptosis of hepatoma cells

Research funding:

摘要

摘要: 目的研究环氧化酶-2（COX-2）反义RNA与塞来昔布联合应用对肝癌细胞（CBRH7919）的抗肿瘤作用。方法观察塞莱昔布对肝癌细胞株CBRH7919、CBRH7919-E及CBRH7919-A（转染反义COX-2基因片段组）体外抗增殖活性、细胞周期及凋亡的影响。通过MTT法、细胞周期分析、RT-PCR等方法测定肝癌细胞株体外增殖的变化。计量资料多组间比较采用多因素方差分析,进一步两两比较采用SNK-q检验。结果加入塞来昔布作用各组细胞后,CBRH7919-A细胞较CBRH7919和CBRH7919-E细胞生长速度明显减慢（F=38. 303,P <0. 01）,且对塞来昔布具有时间、剂量依赖性（F值分别为162. 638、22. 666,P值均<0. 01）。塞莱昔布能够明显提高G0/G1比例,对S期细胞有显著的抑制作用,且具有剂量依赖性（F=32. 515,P <0. 01）,而G2/M变化不明显。CBRH7919-A细胞较CBRH7919,CBRH7919-E细胞对塞来昔布作用更敏感（F=1219. 506,P <0. 01）。加入不同浓度的塞来昔布后（4...
- 癌,肝细胞 /
- 环氧化酶2 /
- 环氧化酶2抑制剂 /
- 细胞增殖 /
- 细胞凋亡
Abstract: Objective To investigate the antitumor effect of cyclooxygenase-2 (COX-2) antisense RNA combined with celecoxib on hepatoma CBRH7919 cells. Methods The effect of celecoxib on in vitro proliferative activity, cell cycle, and apoptosis of hepatoma cell lines CBRH7919, CBRH7919-E, and CBRH7919-A (transfected with COX-2 antisense gene segment) were observed. MTT assay, cell cycle analysis, and RT-PCR were used to evaluate the change in in vitro proliferation of hepatoma cell lines. A multivariate analysis of variance was used for comparison of continuous data between groups, and the SNK-q test was used for further comparison between two groups.Results After the treatment with celecoxib, CBRH7919-A cells had a significant reduction in growth rate compared with CBRH7919 and CBRH7919-E cells (F = 38. 303, P < 0. 01) , in a time-and dose-dependent manner (F = 162. 638 and 22. 666, both P < 0. 01) .Celecoxib significantly increased the proportion of cells in G0/G1 phase and had a marked inhibitory effect on cells in S phase in a dose-dependent manner (F = 32. 515, P < 0. 01) , while there was no significant change in the proportion of cells in G2/M phase. Compared with CBRH7919 and CBRH7919-E cells, CBRH7919-A cells were more sensitive to celecoxib (F = 1219. 506, P < 0. 01) . After the treatment with celecoxib at different concentrations (40 and 80 μmol/L) , all three groups had a significant increase in cell apoptosis (all P <0. 01) , and there was no significant difference in apoptosis between the three groups (P > 0. 05) . Conclusion COX-2 antisense RNA combined with celecoxib can inhibit the in vitro growth and proliferation and cell cycle of hepatoma CBRH7919 cells, promote apoptosis, and thus exert a potential therapeutic effect on hepatoma cells.
- carcinoma, hepatocellular /
- cyclooxygenase 2 /
- cyclooxygenase 2 inhibitors /
- cell proliferation /
- apoptosis

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参考文献(18)

[1] ZHAO XQ, JIANG HC, ZOU YN, et al. Experimental study on the inhibitory effect of selexib on hepatocellular carcinoma[J]. Chin J Hepatobiliary Surg, 2006, 12 (5) :350-351. (in Chinese) 赵宪琪, 姜洪池, 邹亚男, 等.塞莱昔布对肝癌细胞抑制作用的实验研究[J].中华肝胆外科杂志, 2006, 12 (5) :350-351.

[2] ZHAO XQ, JIANG HC, PIAO DX, et al. COX-2 antisense RNA inhibit the proliferation of hepatocellular carcinoma cells study[J]. Chin J Hepatobiliary Surg, 2009, 15 (12) :912-916. (in Chinese) 赵宪琪, 姜洪池, 朴大勋, 等. COX-2反义RNA抑制肝癌细胞增殖的实验研究[J].中华肝胆外科杂志, 2009, 15 (12) :912-916.

[3] BONNVAS S, TSANTES A, DROSOS T, et al. Cancer chemoprevention:A summary of the current evidence[J]. Anticancer Res, 2008, 28 (3B) :1857-1866.

[4] CHENG J, JMANISHI H, AMURO Y, et al. NS-398, a selective cyclooxygenase 2 inhibitor, inhibited cell growth and induced cell cycle arrest in human hepatocellular carcinoma cell lines[J]. Int J Cancer, 2002, 99 (5) :755-761.

[5] CUI W, YU CH, HU KQ, et al. In vitro and in vivo effects and mechanisms of celecoxib-induced growth inhibition of human hepatocellular carcinoma cells[J]. Clin Cancer Res, 2005, 11 (22) :8213-8221.

[6] MAIERT, SCHILINGK, SCHMIDT R, et al. Cyclooxygenase-2 (COX-2) -dependent and-independent anticarcinogenic effects of celecoxib in human colon carcinoma cells[J]. Biochem Pharmacol, 2004, 67 (8) :1469-1478.

[7] PATAL V, DUNN M, SOROKIN A. Regulation of MDR-1 (P-glycoprotein) by cyclooxygenase-2[J]. J Biol Chem, 2002, 277:38915-38920.

[8] KUROKAWA T, KOHNO K, NAGAI K, et al. Antisense RNA transcripts in the blood may be novel diagnostic markers for colorectal cancer[J]. Oncol Lett, 2017, 14 (3) :3487-3493.

[9] LAI YX, XU P, LIU J, et al. Decreased expression of the long non-coding RNA MLLT4 antisense RNA 1 is a potential biomarker and an indicator of a poor prognosis for gastric cancer[J]. Oncol Lett, 2017, 14 (3) :2629-2634.

[10] MIN SN, WEI T, WANG XT, et al. Clinicopathological and prognostic significance of homeobox transcript antisense RNA expression in various cancers:A meta-analysis[J]. Medicine (Baltimore) , 2017, 96 (23) :e7084.

[11] SAVITSKA M, ONISHCHENKO G. Mechanisms of Apoptosis[J].Biochemistry Mosc, 2015, 80 (11) :1393-1405.

[12] LI Q, PENG J, LIU T, et al. Effects of celecoxib on cell apoptosis and Fas, Fas L and Bcl-2 expression in a BGC-823 human gastric cancer cell line[J]. Exp Ther Med, 2017, 14 (3) :1935-1940.

[13] KUMAR V, KAUR K, GUPTA G, et al. Developments in synthesis of the anti-inflammatory drug, celecoxib:A review[J]. Recent Pat Inflamm Allergy Drug Discov, 2013, 7 (2) :124-134.

[14] CHEN J, SHENG P, ZHANG XC, et al. Efficacy and safety profile of celecoxib for treating advanced cancers:A meta-analysis of 11randomized clinical trials[J]. Clin Ther, 2014, 36 (8) :1253-1263.

[15] CHE XH, CHEN CL, YE XL, et al. Dual inhibition of COX-2/5-LOX blocks colon cancer proliferation, migration and invasion in vitro[J]. Oncol Rep, 2016, 35 (3) :1680-1688.

[16] WINTHER T, TORP S. The anti-apoptotic protein survivin can improve the prognostication of meningioma patients[J]. PLo S One, 2017, 12 (9) :e0185217.

[17] YU TT, LAO XZ, ZHENG H, et al. Influencing COX-2 Activity by COX related pathways in inflammation and cancer[J]. Mini Rev Med Chem, 2016, 16 (15) :1230-1243.

[18] MORIA L, CASTELLSA. Cyclooxygenase as a Target for Colorectal Cancer Chemprevention[J]. Curr Drug, 2011, 12 (13) :1888-1894.

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