摘要
目的探讨免疫抑制剂对肝癌细胞增殖、运动侵袭能力的影响,为肝癌肝移植术后免疫抑制剂的选用提供指导。方法用裸鼠人高转移肝癌模型LCI-D20,研究环孢素A(CsA)、他克莫司(FK506)、雷帕霉索(RPM)对肿瘤生长及自发肺转移的影响。采用扫描电镜、噻唑蓝比色法 (MTT)、流式细胞仪、Boyden小室等方法分别研究各免疫抑制剂对人肝癌高转移细胞株 MHCC97H增殖、凋亡、细胞周期、运动及侵袭的影响。结果体内实验中,RPM抑制了LCI-D20 模型移植瘤的生长[(0．76±0．38)g vs(2．09±0．75)g,P<0．05]及肺转移的发生(2／7 vs．7／7, P<0．05);CsA组肺部转移灶的数目明显多于对照组(6±2 vs．4±1,P<0．05);FK506组肺转移发生率虽较对照组减少,但差异无统计学意义。CsA及FK506均对移植瘤的生长无影响。体外实验中,RPM抑制了MHCC97H增殖,并使细胞周期停滞于G_0-G_1期。RPM及FK506抑制了 MHCC97H的运动、侵袭(P<0．05),而CsA则促进了MHCC97H的运动、侵袭(P<0．05)。结论 CsA促进了肝癌的转移;FK506不促进肝癌的转移;而RPM则抑制了肝癌细胞的增殖及转移。
Objective To explore the effects of immunosuppressants on proliferation, invasion and metastasis abilities of hepatocellular carcinoma ceils. Methods The effects of immunosuppressants on tumor growth and metastasis were investigated in LCI-D20 nude mice model with a highly-potentiaUy human hepatoceUular carcinoma. Their effects on phenotypic changes, proliferation, apoptosis, cell cycles, motility and invasiveness on MHCC97H cell line were also studied in vitro by scanning dectron microscopy, MTT, flow cytometry, Boyden chamber methods. Results In vivo, rapamycin inhibited tumor growth and lung metastasis compared with control in nude mice [ （0.76 ±0.38） g vs （2.09± 0.75） g, 2/7 vs 7/7, P〈 0.05]. The number of metastatic nodules in lung was increased in cyclospotine group as compared with control group （6 ± 2 vs 4± 1, P〈 0.05）. There was no significant difference between FK506 and control in lung metastasis rate （5/7 vs 7/7, P 〉0.05）. In vitro, treatment of MHCC97H resuited in striking morphological alterations in Cyclosporine group, including numerous pseudopodial protrusions, increased ceil motility, and metastasis abilities. FK506 and rapamycin inhibited motility and invasiveness of MHCC97H in Boyden chamber assay. Rapamycin also inhibited the growth of MHCC97H and caused G0-G1 arrest. Conclusion Cyclosporine promoted hepatoceilular carcinoma ceil progress/on, FK506 did not promote hepatoceilular carcinoma ceil invasiveness at least, and rapamycin inhibited growth, motility and invasiveness of hepatoceilular carcinoma ceils.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2006年第3期291-292,共2页
Chinese Journal of Experimental Surgery
基金
上海市科学技术委员会资助项目(044119608)
关键词
免疫抑制剂
癌
肝细胞
肿瘤
转移
Immunosuppressant
Carcinoma, hepatoceUular
Neoplasm, metastasis
