【摘要】 目的研究应用α干扰素 （Ｉｎｔｅｒｆｅｒｏｎ－ α ， ＩＦＮ－ α）对根治性切除术后肝癌转移复发的抑制作用，以及联合应用全反式维甲酸（ａｌｌ ｔｒａｎｓ ｒｅｔｉｎｏｉｃ ａｃｉｄ， ＡＴＲＡ）是否与ＩＦＮ－α的疗效有协同作用。方法在体外检测ＩＦＮ－α和（或）ＡＴＲＡ对肝癌细胞株ＳＭＭＣ７７２１、ＢＥＬ－７４０２、ＢＥＬ－７４０５、ＭＨＣＣ９７增殖的影响。４４只裸鼠肝内原位接种裸鼠人肝癌转移模型ＬＣＩ－Ｄ２０肿瘤组织，于种植后第１０天切除移植瘤，共分５组，分别为ＩＦＮ－α治疗组（皮下注射， ３×１０５ Ｕ·只一１· ｄ－１） ８只裸鼠， ＩＦＮ－ａ治疗组（６ × １０５ Ｕ·只一１· ｄ－１） ８只裸鼠， ＡＴＲＡ治疗组（灌胃， ２０ ｍｍ· ｋｇ－１· ｄ－１） ８只裸鼠， ＩＦＮ－α联合 ＡＴＲＡ治疗组（ ２０ ｍｍ· ｋｇ－１· ｄ－１灌胃， ＩＦＮ－α ６×１０５ Ｕ·只－１· ｄ－１皮下注射） ８只裸鼠，对照组 １２只裸鼠。于切除后第 ２天开始用药，治疗 ３５ ｄ后处死动物，测量复发瘤大小，观察肝内播散、肝外转移情况。结果 体外实验表明ＩＦＮ－α和ＡＴＲＡ抑制肝癌细胞的增殖作用不明显。对照组裸鼠肺转移率为 １００％（１２／１２）、肝内复?更多还原

【Abstract】 Objective To study the effect of interferon- α (IFN- α ) on the recurrence and metastasis of hepatocellular carcinoma (HCC) in nude mice, and to clarify if there is synergistic effect treated by combination of IFN-α and all-trans retinoic acid (ATRA). Methods The effect of IFN- α and/or ATRA on the proliferation of HCC cell lines was measured in vitro. The metastatic model of human HCC in nude mice LCI-D20 was used in present study. Curative resection was performed at 10th day after implantation in 44 nude mice. Drugs were given at the next day after resection. IPN- α was administered subcutaneously at doses of 3 x 105 U/day, 6 x 105 U/day, respectively. ATRA was administered p.o. at a dose of 20mg .kg-1. day-1, and IFN-α 6 x 105 U/day combined with ATRA 20mg·kg-1. day-1. The mice were sacrificed 35 days after treatment. The recurrent tumor size was measured and the presence of intrahepatic dissemination and lung metastases were recorded. Results The effect of IFN- α and/or ATRA on the proliferation of HCC cells SMMC7721, BEL-7402, BEL-7405, and MHCC97 was not obvious. The combination of IFN- α and ATRA had no synergistic effect in vitro. The lung metastatic rate, the liver recurrent rate, the size of main recurrent lesions, the number of intrahepatic disseminating nodules and the largest disseminating nodule of the controlled group was 100%(12/12), 100%(12/12), (1346.3 ±4.2 )mm3, 8.2 ± 4.4, 864 mm3, respectively; whereas it was 0, 87.5%(718), (8.7 / 2.9) mm3, 2.3 ± 0.6, and 7.8 mm3, respectively in the IFN-α 3 x 105U/day treated group(P<0.05); 0, 12.5%(1/8), 0.5 mm3, 2, 0.5 mm3 in the IFN- α 6 x 105U/day treated group(p <0.05); 0, 12.5%(1/8), 1 mm3, 2.5 ± 0.7, 8 mm3 in the IFN- α 3 x 105U/day and ATRA treated group(P<0.05); 87.5%, 100%, (1472.6± 5.6) mm3, 7.3 ± 3.8, 768.5 mm3 in the ATRA treated group (P>0.05). Conclusions IFN- α has an inhibitory effect on intrahepatic recurrence and lung metastasis of human HCC after curative resection in nude mice, and the effect is enhanced with increasing dose. IFN- α and ATRA have no synergistic effect according to in vivo and in vitro test. ATRA has no effect on recurrence and metastasis of HCC.更多还原