32种新硫色满酮衍生物对肿瘤细胞的细胞毒作用及其作用机制分析 word格式.docxVIP

摘要摘要本文对 32 种新合成的硫色满酮衍生物的体外抗肿瘤活性进行了研究，采用 MTT 法 检测对 12 种人源肿瘤细胞系（A549，SGC-7901，BGC-823，U937，K562，Hela，MCF-7， HepG-2，A375，LS174T，HT1080，786O）、1 种鼠源肿瘤细胞系(S180)以及人胚肺成纤 维细胞（MRC-5）增殖的影响。其中 6 个化合物（18 号-22 号及 45 号）对 11 种肿瘤细 胞的 IC50 在 1.3-49.0μM 之间；4 个化合物（23 号、24 号、29 号和 30 号）对 7 种肿瘤 细胞的 IC50 在 1.39-21.04μM 之间；6 个化合物（50 号-54 号及 59 号）对 10 种肿瘤细胞 的 IC50 在 1.3-37.0μM 之间；2 个化合物（CMDMT 和 CMDCT）对 6 种肿瘤细胞的 IC50 在 8.34-24.29μM 之间；剩余 14 个化合物活性较低或对肿瘤细胞生长无抑制作用。18 种 化合物能够明显抑制肿瘤细胞的生长，其抑制率明显高于同浓度顺铂（CDDP），具有 极高的抗肿瘤活性，本实验为深入研究这些化合物的体内抗肿瘤作用提供了有力的实验 数据。本研究对其中一个代表性化合物（顺）-3（氯代亚甲基）-5，7-二甲基-硫色满-4- 酮(CMDMT)诱导 HepG-2 细胞凋亡的机制进行了初步探讨。采用台盼蓝染色细胞计数法 测定 CMDMT 作用后 HepG-2 细胞存活率，绘制细胞生长曲线；TUNEL 法形态学观察 CMDMT 对 HepG-2 细胞凋亡的影响；流式细胞术（FCM）检测 HepG-2 细胞的凋亡率； ELISA 法检测细胞内 caspase-3 的含量。结果表明 CMDMT 以浓度依赖方式诱导 HepG-2 细胞凋亡。关键词硫色满酮衍生物MTT 法抗肿瘤活性半数抑制浓度细胞凋亡Caspase-3AbstractAbstractWe have investigated the anti-proliferative activities of 32 Novel synthesized Thiochromanone Derivatives in vitro. MTT assay was used to test the inhibitory effect of 32 compounds on 13 tumor cell lines. 6 tested chemicals (18-22 45) showed cell toxicity to 11 human tumor cell lines ( A549, SGC-7901, BGC-823, K562,U937, Hela, MCF-7, HepG-2, A375, LS174T, HT1080 786O ), and the half maximal inhibitory concentration ( IC50 )values were between 1.3-49.0μM. 4 tested chemicals (23, 24, 29, 30) showed excellentactivities against the 7 human tumor cell lines in vitro, the half maximal inhibitory concentration (IC50) were between 1.39-21.04μM; 6 tested chemicals (50-54 59) showed cell toxicity to 10 human tumor cell lines, and the half maximal inhibitory concentration( IC50 ) values were between 1.3-37.0μM. 2 tested chemicals(CMDMT CMDCT) showedthe inhibitory effect on 6 human tumor cell lines, and the half maximal inhibitory concentration ( IC50 ) values were between 8.34-24.29μM. The inhibition effects of the chemicals on tumor cells were much higher than cisplatin at the same concentration. Theother 14 chemicals have no effects on the growth of human