维甲酸对胰腺癌细胞生长的抑制作用及其机制研究

The mechanisms of inhibitory effect of retinoic acid on human pancreatic carcinoma cells

目的：观察两种维甲酸（ ＲＡ） 对人胰腺癌细胞生长的抑制作用及其可能机制。方法：应用ＭＴＴ 比色法、流式细胞仪、裸鼠肾包膜下移植瘤抑制试验和透射电镜技术进行检测。结果：ＲＡ 抑制胰腺癌细胞生长，６ ｄ 组抑制５０ ％细胞生长的药物浓度（ＩＣ５０） 全反式ＲＡ（ＡＴＲＡ） 和１３ － 顺式（ＣＲＡ） 分别为１０ ～３０ μｍｏｌＬ 和３０ ～５０ μｍｏｌＬ。癌细胞在ＲＡ作用下，Ｇ０／Ｇ１ 期细胞比例增加，Ｓ 期细胞比例和增殖指数（ＰＩ） 下降。ＡＴＲＡ ６ ｄ 组凋亡指数（ ＡＩ） 增高，ＡＴＲＡ 和ＣＲＡ ６ ｄ组ＡＩＰＩ 比例分别是对照组的４ 倍和２ 倍。ＡＴＲＡ 能显著抑制肾包膜下胰腺癌移植瘤生长，电镜检查证实部分胰腺癌细胞具有凋亡特征。结论：ＲＡ

AIM:To investigate the mechanisms of two kinds of retinoic acid (RA) on the growth inhibition of human pancreatic carcinoma cells. METHODS:MTT colorimetric assays, flow cytometric analysis, subrenal capsule(SRC) xenograft assay in nude mice and transmission electron microscopy were performed. RESULTS:RA inhibited the growth of pancreatic caricinoma cells. The 50% inhibitory concentration (IC 50 ) of all-trans RA(ATRA) and 13-cis RA(CRA) on cell growth occurred after 6d induction were 10～30 μmol/L and 30～50 μmol/L respectively. RA increased the precentage of cell population in the G 0/G 1 phase ,but reduced it in S phase and also reduced proliferation index (PI). Cell apoptosis index (AI) was higher in 6d ATRA treated group than control group. AI/PI of ATRA and CRA 6d treated group were 4 and 2 times as control group. ATRA inhibited significantly growth of SRC pancreatic carcinoma. The morphology of ATRA treated cells was primarily characterized by apoptosis. CONCLUSION:The antitumor effects of RA are primarily related to the inhibition of proliferation of pancreatic carcinoma cells.