CAJ | 학술논문

背景与目的：近来发现，临床上常用的非甾体类抗炎药(non-steroidal anti-inflammatory drugs， NSAIDs)可以降低多种癌症的发病率。布洛芬(ibuprofen)作为一种常用的NSAIDs，对肝癌是否具有抑制作用，国内外鲜有报道。本研究初步探讨布洛芬抑制肝癌细胞BEL-7402的作用，并研究其相关机制。方法：肝癌细胞BEL-7402分为对照组和不同浓度布洛芬处理组，药物处理0、24、48和72 h后用MTT法检测各组细胞增殖抑制率；流式细胞术检测各组细胞的周期分布；细胞分析仪检测各组细胞活力及细胞凋亡；蛋白[质]印迹(Western blot)检测各组细胞增殖性核抗原(PCNA)、细胞周期蛋白(Cyclin D1)、B细胞淋巴瘤/白血病-2(Bcl-2)和环氧合酶-2(COX-2)蛋白的表达；ELISA法检测细胞培养上清液中前列腺素E2(PGE2)蛋白表达水平。结果：布洛芬组中BEL-7402细胞增殖受到抑制，且抑制作用呈时间和剂量依赖性(P<0.05)。2.0 mmol/L布洛芬组48 h细胞活力明显低于对照组[(47.87±5.23)%vs (88.93±5.49)%]，G0/G1期细胞比例明显高于对照组[(80.04±3.61)%vs (62.36±8.33)%]，细胞早期凋亡率明显高于对照组[(36.65±10.07)% vs (9.81±6.80)%]，差异有统计学意义(P<0.05)。布洛芬作用于细胞48 h后，PCNA、Cyclin D1、Bcl-2以及COX-2蛋白表达与对照组相比显著减少(P<0.05)；细胞培养上清液中PGE2蛋白表达量与对照组[(23.98±4.89) ng/L vs (68.70±9.43) ng/L]相比，显著降低(P<0.01)。结论：布洛芬能够抑制肝癌细胞BEL-7402增殖与活力，阻滞细胞周期，促进细胞凋亡，其作用机制可能与抑制COX-2及PGE2表达有关。
배경여목적：근래발현，림상상상용적비치체류항염약(non-steroidal anti-inflammatory drugs， NSAIDs)가이강저다충암증적발병솔。포락분(ibuprofen)작위일충상용적NSAIDs，대간암시부구유억제작용，국내외선유보도。본연구초보탐토포락분억제간암세포BEL-7402적작용，병연구기상관궤제。방법：간암세포BEL-7402분위대조조화불동농도포락분처리조，약물처리0、24、48화72 h후용MTT법검측각조세포증식억제솔；류식세포술검측각조세포적주기분포；세포분석의검측각조세포활력급세포조망；단백[질]인적(Western blot)검측각조세포증식성핵항원(PCNA)、세포주기단백(Cyclin D1)、B세포림파류/백혈병-2(Bcl-2)화배양합매-2(COX-2)단백적표체；ELISA법검측세포배양상청액중전렬선소E2(PGE2)단백표체수평。결과：포락분조중BEL-7402세포증식수도억제，차억제작용정시간화제량의뢰성(P<0.05)。2.0 mmol/L포락분조48 h세포활력명현저우대조조[(47.87±5.23)%vs (88.93±5.49)%]，G0/G1기세포비례명현고우대조조[(80.04±3.61)%vs (62.36±8.33)%]，세포조기조망솔명현고우대조조[(36.65±10.07)% vs (9.81±6.80)%]，차이유통계학의의(P<0.05)。포락분작용우세포48 h후，PCNA、Cyclin D1、Bcl-2이급COX-2단백표체여대조조상비현저감소(P<0.05)；세포배양상청액중PGE2단백표체량여대조조[(23.98±4.89) ng/L vs (68.70±9.43) ng/L]상비，현저강저(P<0.01)。결론：포락분능구억제간암세포BEL-7402증식여활력，조체세포주기，촉진세포조망，기작용궤제가능여억제COX-2급PGE2표체유관。
Background and purpose:Recently, studies showed that non-steroidal anti-inlfammatory drugs (NSAIDs) could reduce the incidence of cancer. Whether ibuprofen could inhibit the growth of hepatocellular carcinoma cells had not been reported yet. In the current study, we investigated the effects of ibuprofen on hepatoma carcinoma BEL-7402 cells and the relevant mechanisms. Methods: Hepatocellular carcinoma BEL-7402 cells were randomly divided into 7 groups:the control group and the ibuprofen groups (0.1, 0.5, 1.0, 2.0, 3.0 and 4.0 mmol/L). The effect of ibu-profen on BEL-7402 HCC cells was measured by MTT method, the cell cycles were analyzed by flow cytometry (FCM), cell vitality and apoptosis were determined by cell analyzer. PCNA, Cyclin D1, Bcl-2 and COX-2 protein levels were examined by Western blot, and the expressions of prostaglandin E2 (PGE2) were measured by ELISA. Results:After the exposure to ibuprofen, the suppression ratio of BEL-7402 cells was increased (P<0.05). BEL-7402 cell vitality was decreased by degrees significantly (P<0.05), early apoptosis of BEL-7402 cells was increased (P<0.05), and the G0/Gl phase ratio was increased significantly compared with control group (P<0.05). Ibuprofen effectively decreased PCNA, Cyclin D1, Bcl-2 and COX-2 expressions in BEL-7402 cells (P<0.05), and decreased PGE2 protein expression in cell culture supernatants sig-nificantly (P<0.05). Conclusion:Ibuprofen is effective for inhibiting the proliferations, increasing apoptosis and blocking cell cycles of BEL-7402 HCC cells. The anti-tumor mechanisms of ibuprofen may be related with the inhibition of COX-2 and PGE2 expressions.