中文摘要：

目的：体外观察FTY720对人卵巢癌细胞的生长抑制效应，探讨其独特的抗癌效应。方法：采用Mr丌法检测不同浓度（2．5，5，7．5，10，12．5，15μmol／L）FTY720作用24、48、72h后，对人卵巢癌OV2008和SKOV3细胞的生长抑制效应。以不同密度（亚饱和、饱和、过饱和）接种OV2008和SKOV3细胞，MTＴ及相差显微镜下检测细胞的形态学，并观察FTY720的抗卵巢癌效应与细胞接种密度间的关系。相差显微镜下观察FTY720诱导的可逆性自噬现象。Westernblot法检测自噬效应分子LC3的表达变化。MTT及Westernblot法分别检测mTOR抑制剂雷帕霉素（RA）、PP2A抑制剂冈田酸（OA）对FTY720抗癌效应的影响。结果：FTY720对卵巢癌OV2008、SKOV3细胞的生长抑制作用呈剂量时间依赖性，且其诱导的卵巢癌细胞毒性效应具有细胞接种密度依赖性。FTY720导致的卵巢癌细胞自噬具有可逆转性特点。RA不影响FTY720的抗卵巢癌效应，而OA则可协同FTY720的抗癌效应。结论：FTY720抑制卵巢癌细胞生长具有剂量时间依赖性，FTY720诱导的细胞密度依赖性抗癌效应、可逆性自噬现象、非mTOR途径依赖，以及其与PP2A途径发生协同抗癌效应等特点提示FTY720独特模式的抗卵巢癌效应。

英文摘要：

Objective：To investigate the cytotoxicity and unique anticancer effect of FTY720 against human ovarian cancer cells. Methods：The human ovarian cancer OV2008 and SKOV3 cells were cultured with different concentration （2.5,5,7.5,10,12.5,15 μmol/L） of FTY720 for indicated time （24,48,72h）. The anticancer activity of FTY720 was measured by MTT. The correlation between FTY720-induced cytotoxicity and cell-seeding density was exam- ined by MTF, further confirmed by morphological alteration with phase-contrast microscope. The reversible phenomenon of FTY720-triggered autophagy was examined by phase-contrast micro- scope and further confirmed by molecular change with Western blot. The influence of signal pathway mTOR or PP2A on the FTY720-induced antieancer effect was examined by MTT and Western blot in the presence or absence of Rapamyein （mTOR inhibitor） or Okadaic acid （OA, PP2A inhibitor）. Results ： FTY720-induced cytotoxicity against human ovarian cancer cell OV2008 and SKOV3 was dose-and time-dependent,also the obvious correlation between cyto-toxicity and cell-seeing density was found. The reversible phenomenon of FTY720-triggerd auto- phagy could be examined by morphological change and molecular alteration. The anticancer effect of FTY720 couldn＇t be influenced by rapamycin but was synergistically enhanced in the presence of OA. Con~lusion：FTY720 can inhibit proliferation of human ovarian cancer cells in a dose-and time-dependent manner, further, the characteristics of FTY720-induced effect such as the obvious correlation between cytotoxicity and cell-seeding density, reversible autophagy as well as the mechanism of roTOR-independent but synergism with PP2A pathway indicate FTY720 can exert its unique anticancer activity against human ovarian cancer.