FTY720诱导卵巢癌细胞发生可逆性白噬及抗癌机制的探索 |
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引用本文: | 季芳,张宁,季雯婷,唐中园,李姝,狄文.FTY720诱导卵巢癌细胞发生可逆性白噬及抗癌机制的探索[J].现代妇产科进展,2013(10):782-786. |
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作者姓名: | 季芳 张宁 季雯婷 唐中园 李姝 狄文 |
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作者单位: | [1]上海交通大学医学院附属仁济医院妇产科妇产科学研究所 [2]上海市妇科肿瘤重点实验室 [3]上海市教委重点学科,上海200127 |
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基金项目: | 上海市卫生局课题(No:2009060);国家自然科学基金面上项目(No:81072137);国家自然科学基金青年项目(No:81101972);上海交通大学医学院院基金(No:11XJ21018) |
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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。
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关 键 词: | 卵巢癌细胞 FTY720 细胞自噬 可逆转性 PP2A |
Reversible autophagy triggered by FTY720 and the exploration of its anticancer mecha-nism against human ovarian cancer cells |
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Institution: | Ji Fang, Zhang Ning, Ji Wenting, et al. (Department of Obstetrics and Gynecology; Institute of Obstetrics and Gynecology, Key Laboratory of Gynecolog- ic Cancer Shanghai Municipality ,Key Discipline of Shanghai Municipal Education Commission, Renji Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai 200127) |
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Abstract: | 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. |
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Keywords: | Ovarian cancer FTY720 Autophagy Reversible PP2A |
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