中国癌症杂志
中國癌癥雜誌
중국암증잡지
CHINA ONCOLOGY
2013年
1期
17-25
,共9页
何利兵%王险峰%王红胜%杜军%张继民
何利兵%王險峰%王紅勝%杜軍%張繼民
하리병%왕험봉%왕홍성%두군%장계민
姜黄素衍生物%结直肠癌%增殖%迁移%凋亡
薑黃素衍生物%結直腸癌%增殖%遷移%凋亡
강황소연생물%결직장암%증식%천이%조망
Curcumin derivatives%Colorectal cancer%Proliferation%Migration%Apoptosis
背景与目的:姜黄素(curcumin)是从天然植物姜黄中提取的酚类化合物,已证实其具有抗恶性肿瘤作用.近年人工合成的姜黄素衍生物被认为抗癌作用和生物利用度优于母体姜黄素,但是对于结肠癌细胞的作用鲜见报道.研究旨在比较天然植物姜黄素及其4种人工合成的衍生物T316、T62、T63、T6F4对结直肠癌细胞株Lovo和SW480的细胞毒性作用、增殖迁移抑制作用和核转录因子(NF-κB)活性表达的影响.方法:培养人结肠癌细胞系Lovo和SW480,然后通过MTT分析检测姜黄素及4种衍生物对结肠癌细胞株Lovo和SW480细胞毒性影响;细胞划痕实验检测对结肠癌细胞迁移抑制作用;软琼脂克隆形成实验检测对癌细胞克隆增殖影响;流式细胞技术检测对癌细胞凋亡的影响;并通过荧光素酶双报告基因法检测姜黄素及其衍生物对NF-κB活性表达的影响.结果:姜黄素对Lovo和SW480的半数有效抑制浓度(IC50)分别为(14.2±0.2)μmol/L和(10.6±0.7)μmol/L,分别是4种衍生物对Lovo和SW480的7.0~8.7倍和5.7~7.8倍(P<0.01).不加任何药物时,Lovo 24 h迁移距离为(160.7±18.4)μm,SW480为(389.9±8.9)μm,但加入姜黄素及4种衍生物后,细胞迁移距离均明显缩短,距离最短是T63作用于Lovo时的(53.2±11.7)μm;T316作用于SW480时的(80.4±9.6)μm.4种衍生物的迁移距离明显短于姜黄素的迁移距离(P<0.05).4种衍生物在抑制2株结肠癌细胞克隆形成方面也明显优于姜黄素母体(P<0.05).通过流式细胞检测发现,姜黄素及4种衍生物诱导Lovo的凋亡率分别为(10.05±0.54)%、(55.32±2.86)%、(31.83±0.85)%、(26.01±0.44)%、(21.44±3.01)%,高于对照组的凋亡率(6.98±0.23)%(P<0.05);且4种衍生物诱导凋亡作用优于姜黄素(P<0.05).荧光素酶报告基因检测结果表明,姜黄素及其4种衍生物能下调TNF-α诱导的NF-κB的转录活性.结论:姜黄素和4种衍生物均能抑制结直肠癌细胞的增殖迁移力,促进结直肠癌细胞的凋亡,但4种衍生物的作用明显优于母体姜黄素.
揹景與目的:薑黃素(curcumin)是從天然植物薑黃中提取的酚類化閤物,已證實其具有抗噁性腫瘤作用.近年人工閤成的薑黃素衍生物被認為抗癌作用和生物利用度優于母體薑黃素,但是對于結腸癌細胞的作用鮮見報道.研究旨在比較天然植物薑黃素及其4種人工閤成的衍生物T316、T62、T63、T6F4對結直腸癌細胞株Lovo和SW480的細胞毒性作用、增殖遷移抑製作用和覈轉錄因子(NF-κB)活性錶達的影響.方法:培養人結腸癌細胞繫Lovo和SW480,然後通過MTT分析檢測薑黃素及4種衍生物對結腸癌細胞株Lovo和SW480細胞毒性影響;細胞劃痕實驗檢測對結腸癌細胞遷移抑製作用;軟瓊脂剋隆形成實驗檢測對癌細胞剋隆增殖影響;流式細胞技術檢測對癌細胞凋亡的影響;併通過熒光素酶雙報告基因法檢測薑黃素及其衍生物對NF-κB活性錶達的影響.結果:薑黃素對Lovo和SW480的半數有效抑製濃度(IC50)分彆為(14.2±0.2)μmol/L和(10.6±0.7)μmol/L,分彆是4種衍生物對Lovo和SW480的7.0~8.7倍和5.7~7.8倍(P<0.01).不加任何藥物時,Lovo 24 h遷移距離為(160.7±18.4)μm,SW480為(389.9±8.9)μm,但加入薑黃素及4種衍生物後,細胞遷移距離均明顯縮短,距離最短是T63作用于Lovo時的(53.2±11.7)μm;T316作用于SW480時的(80.4±9.6)μm.4種衍生物的遷移距離明顯短于薑黃素的遷移距離(P<0.05).4種衍生物在抑製2株結腸癌細胞剋隆形成方麵也明顯優于薑黃素母體(P<0.05).通過流式細胞檢測髮現,薑黃素及4種衍生物誘導Lovo的凋亡率分彆為(10.05±0.54)%、(55.32±2.86)%、(31.83±0.85)%、(26.01±0.44)%、(21.44±3.01)%,高于對照組的凋亡率(6.98±0.23)%(P<0.05);且4種衍生物誘導凋亡作用優于薑黃素(P<0.05).熒光素酶報告基因檢測結果錶明,薑黃素及其4種衍生物能下調TNF-α誘導的NF-κB的轉錄活性.結論:薑黃素和4種衍生物均能抑製結直腸癌細胞的增殖遷移力,促進結直腸癌細胞的凋亡,但4種衍生物的作用明顯優于母體薑黃素.
배경여목적:강황소(curcumin)시종천연식물강황중제취적분류화합물,이증실기구유항악성종류작용.근년인공합성적강황소연생물피인위항암작용화생물이용도우우모체강황소,단시대우결장암세포적작용선견보도.연구지재비교천연식물강황소급기4충인공합성적연생물T316、T62、T63、T6F4대결직장암세포주Lovo화SW480적세포독성작용、증식천이억제작용화핵전록인자(NF-κB)활성표체적영향.방법:배양인결장암세포계Lovo화SW480,연후통과MTT분석검측강황소급4충연생물대결장암세포주Lovo화SW480세포독성영향;세포화흔실험검측대결장암세포천이억제작용;연경지극륭형성실험검측대암세포극륭증식영향;류식세포기술검측대암세포조망적영향;병통과형광소매쌍보고기인법검측강황소급기연생물대NF-κB활성표체적영향.결과:강황소대Lovo화SW480적반수유효억제농도(IC50)분별위(14.2±0.2)μmol/L화(10.6±0.7)μmol/L,분별시4충연생물대Lovo화SW480적7.0~8.7배화5.7~7.8배(P<0.01).불가임하약물시,Lovo 24 h천이거리위(160.7±18.4)μm,SW480위(389.9±8.9)μm,단가입강황소급4충연생물후,세포천이거리균명현축단,거리최단시T63작용우Lovo시적(53.2±11.7)μm;T316작용우SW480시적(80.4±9.6)μm.4충연생물적천이거리명현단우강황소적천이거리(P<0.05).4충연생물재억제2주결장암세포극륭형성방면야명현우우강황소모체(P<0.05).통과류식세포검측발현,강황소급4충연생물유도Lovo적조망솔분별위(10.05±0.54)%、(55.32±2.86)%、(31.83±0.85)%、(26.01±0.44)%、(21.44±3.01)%,고우대조조적조망솔(6.98±0.23)%(P<0.05);차4충연생물유도조망작용우우강황소(P<0.05).형광소매보고기인검측결과표명,강황소급기4충연생물능하조TNF-α유도적NF-κB적전록활성.결론:강황소화4충연생물균능억제결직장암세포적증식천이력,촉진결직장암세포적조망,단4충연생물적작용명현우우모체강황소.
Background and purpose:Curcumin is a phenolic compound extracted from the natural plant turmeric, which confer an antitumor effect. Recently, it was found that some curcumin derivatives also possessed the inhibiting effects on tumor angiogenesis and metastasis, even stronger than curcumin itself. However, no study dealing with their anticancer effect on colorectal cancer cells in vitro has been reported by far. This study aimed to investigate the roles of curcumin and its 4 derivatives, T316, T62, T63, and T6F4 in the proliferation and invasion of human colon cancer cell line Lovo and SW480. Methods:The inhibitory effects of curcumin and novel structural analogues T316, T62, T63, and T6F4 in 2 kinds of human colorectal cancer cell lines, SW480 and Lovo were investigated by MTT-based assay, Scratch-wound assay, soft agar colony formation assay, and flow cytometry. The transcriptional activity of NF-κB promoter was detected by luciferase assay. Results:The IC50 of curcumin were (14.2±0.20)μmol/L and (10.6±0.70) μmol/L on Lovo and SW480, respectively, which were 7.0-8.7 folds, and 5.7-7.8 folds, significantly greater than its 4 derivatives in same cell lines (P<0.01). The results of Scratch-wound assay revealed that there was a significant reduction within 24 h of cell migration distance in 4 derivative-groups compared with the cucurmin group (160.7±18.4)μm for Lovo, and (389.9±8.9)μm for SW480, respectively (P<0.05). Soft agar colony formation assay showed a significant reduction in cloning number of 4 derivative-groups (P<0.05) compared with the cucurmin group (60±8 for Lovo and 75±5 for SW480), respectively. The proportion of apoptosis of Lovo cell exposure to 4 derivatives were (55.32±2.86)%, (31.83±0.85)%, (26.01±0.44)%, (21.44±3.01)%in T316, T62, T63, and T6F4, respectively, which were significantly higher than control (6.81±0.23)%and curcumin group (10.05±0.54)%(P<0.05). Luciferase assays also showed that treatment with curcumin or its 4 derivatives could inhibit NF-κB activation which induced by TNF-α. Conclusion:Curcumin and its 4 derivatives could inhibit proliferation and migration ability of colorectal cancer cells lines Lovo and SW480, and promoted cells apoptosis. Furthermore, the effects of 4 derivatives were significantly stronger than curcumin itself.
