目的探讨一种新的人工半合成紫草萘醌类衍生物(2,3,11-三乙巯基-6-异己萘茜,简称TE ISHNZ)。在体外对8种人癌细胞的细胞毒作用及诱导人鼻咽癌细胞(CNE₂)细胞凋亡的作用。方法应用噻唑蓝(M TT)比色法检测TE ISHNZ对8种人癌细胞的增殖抑制作用,以半数抑制浓度(IC₅₀)为指标进行评价。应用流式细胞术(FCM)检测TE ISHNZ诱导CNE₂细胞凋亡的作用及其对细胞周期的影响。结果TE ISHNZ在0.78~25μg/mL质量浓度下,对8种人癌细胞均有明显的增殖抑制作用;对CNE₂细胞、人肺腺癌细胞(GLC-82)、人肝癌细胞(B e l-7402)、人白血病细胞(K 562)、人宫颈癌细胞(H eL a)、人胃腺癌细胞(mgC-803)、人乳腺癌细胞(M DA 453)和人口腔癌细胞(KB)的IC₅₀分别为3.96、2.48、5.13、1.92、4.54、5.88、1.35和3.44μg/mL,IC₅₀值均在6μg/mL以下。FCM检测结果显示,以TE ISHNZ(1.56、3.12和6.25μg/mL)处理CNE₂细胞48 h后,在FCM的DNA直方图上可见亚二倍体(亚G1峰);细胞凋亡率依次为3.9%、10.8%和28.1%,而对照组的细胞凋亡率为2.2%;TE ISHNZ对CNE₂细胞的诱导凋亡作用呈浓度依赖性;细胞周期分析显示CNE₂细胞被阻滞于G₂/M期。用6.25μg/mL TE ISHNZ处理CNE₂细胞12、24、36和48 h后亦可见细胞凋亡,细胞凋亡率分别为4.5%、27.2%、48.2%和24.9%,而对照组的凋亡率为1.0%。CNE₂细胞被TE ISHNZ处理的前36 h,其凋亡率随着作用时间的延长而增加,被阻于S和G₂/M期;作用48 h时,被阻于G₂/M期。结论TE ISHNZ对多种人癌细胞有明显的细胞毒作用,且能诱导CNE₂细胞凋亡,并使细胞周期阻滞于S期和(或)G₂/M期。

Objective To explore the cytotoxicity on eight kinds of human cancer cell lines and apoptosis induction on human nasopharyngeal cancer cells(CNE₂) of a new semi-synthesized naphthoquinone derivative(2,3,11-triethanesulfanyl-6-isohexenylnaphthazarin,TEISHNZ).Methods Inhibition of TEISHNZ on eight kinds of human cancer cell lines proliferation was assayed using MTT method.The cytotoxicity was evaluated using IC₅₀ value.Apoptosis induction and effect on cell cycle distribution of TEISHNZ on human nasopharyngeal cancer cells were assayed by Flow Cytometry(FCM).Results Under the 0.78-25 μg/mL of concentrations,TEISHNZ had markedly proliferated inhibition on human cancer cell lines.The IC₅₀ values of TEISHNZ on CNE₂,GLC-82,Bel-7402,K562,HeLa,MGC-803,MDA453,and KB cells were 3.96,2.48,5.13,1.92,4.54,5.88,1.35,and 3.44 μg/mL,respectively.The IC₅₀ values were less than 6 μg/mL.CNE₂ cells were treated respectively for 48 h by TEISHNZ(1.56,(3.12),and 6.25 μg/mL) and then the CNE₂ cells were detected by FCM.The result showed sub-G peak,the apoptotic rates were(3.9%),10.8%,and 28.1%,respectively,and apoptotic rates of control group was 2.2%,apoptosis induction of TEISHNZ on CNE₂ cell was in a concentration dependent manner,cell cycle analysis indicated that CNE₂ cells were blocked in G₂/M phase.After treatment with TEISHNZ(6.25 μg/mL) for 12,24,36,and 48 h,CEN₂ cell apoptotic rates were 4.5%,27.2%,48.2%,and 24.9%,respectively,and apoptotic rate of control group was 1.0%.The apoptotic rates increased with longing of treatment time,before CNE₂ cells of treatment for 36 h,CNE₂ cells,were blocked in S and G₂/M phase,after treatment for 48 h,CNE₂ cells blocked in G₂/M phase.Conclusion TEISHNZ against various human carcinoma cells shows marked cytotoxicity and could induce cell apoptosis,and cell cycle arrest at S phase and(or) G₂/M phase.

国家自然科学基金资助项目(20272085,30271601)