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目的研究人α-甘露糖苷酶(hMan2c1)转基因对小鼠移植性肿瘤生长、转移的影响。方法接种肝癌细胞H22或肉瘤细胞S180于野生型ICR小鼠和3个系的转基因小鼠(28、35和54号)右侧腋窝皮下,连续测量肿瘤体积。分别于接种细胞第9天和第10天处死小鼠,称重肿瘤。分别对肿瘤组织和肺组织进行HE染色。用Tris-NH4Cl破碎脾脏中的红细胞,以Yac-1细胞为靶细胞,检测脾脏中自然杀伤(NK)细胞的活性。结果接种于3个系的转基因小鼠的H22肿瘤或S180肿瘤的体积及重量均显著高于野生型小鼠(P<0.05)。绝大多数转基因小鼠的肿瘤向周围组织侵袭,而野生型小鼠的肿瘤几乎均有包膜。54、35和28号转基因小鼠的H22肿瘤肺转移率分别为30%(3/10)、50%(5/10)和30%(3/10),野生型小鼠的肿瘤肺转移率为10%(1/10);54、35和28号转基因小鼠的S180肿瘤肺转移率分别为16.7%(1/6)、50%(3/6)和33.3%(2/6),野生型小鼠的肿瘤肺转移率为0(0/10)。转基因小鼠脾脏的NK细胞活性与野生型小鼠比较差异无显著性(P>0.05)。结论hMan2c1转基因促进移植性H22肿瘤及S180肿瘤在ICR小鼠的生长、侵袭和转移,hMan2c1转基因对小鼠脾脏NK细胞的活性无影响。
Objective To study the effect of human α-mannosidase (hMan2c1) transgene on the growth and metastasis of transplanted tumor in mice. Methods H22 hepatoma cells or S180 cells were inoculated subcutaneously in the right armpit of wild-type ICR mice and 3-line transgenic mice (28, 35 and 54) for tumor volume measurement. Mice were sacrificed on day 9 and day 10, respectively, of the inoculated cells and tumors were weighed. Tumor tissue and lung tissue were stained with HE. Red blood cells in the spleen were disrupted with Tris-NH4Cl and natural killer (NK) cells in the spleen were tested for their ability to target Yac-1 cells. Results The volume and weight of H22 tumor or S180 tumor in transgenic mice inoculated into 3 lines were significantly higher than those in wild type mice (P <0.05). Tumors in the vast majority of transgenic mice invade the surrounding tissues, whereas tumors in wild-type mice have almost all of the tumors. The lung metastasis rates of H22 tumors in transgenic mice of Nos. 54, 35 and 28 were 30% (3/10), 50% (5/10) and 30% (3/10), respectively. The lung metastasis rate Was 10% (1/10); S180 tumor lung metastasis rates of transgenic mice of 54, 35 and 28 were 16.7% (1/6), 50% (3/6) and 33.3% (2/6) Wild-type mice had a tumor lung metastasis rate of 0 (0/10). The spleen NK cell activity of transgenic mice showed no significant difference compared with wild type mice (P> 0.05). Conclusion hMan2c1 transgene promotes the growth, invasion and metastasis of H22 and S180 tumors in ICR mice. The hMan2c1 transgene has no effect on the activity of spleen NK cells in mice.