【摘要】目的:探讨雷公藤内酯醇(TL)对胰腺癌细胞增殖和凋亡的影响及其机制。方法:胰腺癌细胞SW1990与TL共同孵育,采用MTT法观察TL对胰腺癌细胞增殖的抑制作用,以流式细胞仪AnnexinⅤ/碘化丙啶(PI)双染法检测TL对SW1990细胞的凋亡的诱导作用和对细胞周期的干预作用。结果:TL抑制SW1990细胞增殖和促进细胞凋亡,呈现为浓度和时间依赖性,TL阻滞胰腺癌细胞周期于G0/G1期。结论:TL能抑制胰腺癌细胞增殖、诱导细胞凋亡及干预胰腺癌细胞周期,TL具有潜在的肿瘤治疗作用。
【关键词】 胰腺肿瘤;雷公藤内酯醇;细胞凋亡
[Abstract] Objective: To investigate the effects and the possible mechanism of triptolide on the growth and apoptosis of human pancreatic cancer cell in vitro. Methods: The pancreatic cancer cell line SW1990 was treated with triptolide. MTT method was used to determine the inhibitory effect of triptolide on cell proliferation, and flow cytometry (FCM) with AnnexinⅤ-FITC and propidium iodide (PI) staining was used to determine apoptosis induction and blocking effects of triptolide on the cycle proliferation. Results: After the treatment with triptolide, cell proliferation was blocked by triptolide, which showed a significant positive association with the level of triptolide concentration(P<0.01), and the apoptotic rates of SW1990 cells were increased in concentration-dependent and time-dependent manners, and its cell cycle was arrested at G0/G1 phase. Conclusion: Triptolide is able to inhibit proliferation , induce the apoptosis and block cell cycle effect on pancreatic cancer cells. The potential for its treatment is worth further investigating.
[Key words] Pancreatic neoplasm;Triptolide;Apoptosis
雷公藤内酯醇(triptolide,TL)是一种从雷公藤等中分离得到的二萜内酯化合物,有明确的抗炎和免疫抑制作用,新近研究发现它有很强的抗肿瘤活性,并能增强多种细胞毒药物的疗效,TL的水溶性前体物PG490-88,正在前列腺癌患者中进行一期临床试验,具有广阔的应用前景[1]。本研究观察了TL对胰腺癌细胞SW1990增殖和凋亡的影响以及对胰腺癌细胞周期的阻滞作用,探讨TL作为胰腺癌的化学治疗药物的可能性。
1 材料与方法
1.1 材料
1.1.1 细胞培养
胰腺癌细胞SW1990由上海交通大学附属第一人民医院消化内科王兴鹏教授惠赠。细胞以含有10%小牛血清的DMEM培养基(Gibco)于37 ℃恒温、5%CO2培养箱中培养,培养基中另加入100 U/ml青霉素、0.1 mg/ml链霉素,2~3 d传代1次。
1.1.2 试剂及器材
TL由中国协和医科大学皮肤病研究所药物研究室马鹏程教授惠赠。二甲亚砜(DMSO)(上海晶美生物公司)。流式细胞仪(FACScalibur型)(美国BD公司)。激光共聚焦扫描显微镜(德国Leica公司)。酶标仪(ELX800通用型)(美国BIO-TEK公司)。Annexin V
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