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目的研究内皮抑素(Es)瘤内与尾静脉两种给药途径联合腹腔注射阿霉素(Adm)对小鼠H22肝癌细胞移植瘤血管生成和肿瘤生长的抑制作用。方法将H22肝癌细胞接种到40只小鼠的背部皮下,肿瘤直径约1cm时按体重随机分成4组;对照组:隔日瘤内、腹腔注射生理盐水;Es瘤内组:隔日瘤内注射Es+腹腔注射Adm;Es静脉组:隔日静脉推注Es+腹腔注射Adm;Adm组:隔日静脉推注生理盐水+腹腔注射Adm。每3d测量皮下肿瘤直径,绘制肿瘤生长曲线,第15天每组处死5只小鼠,检测血浆VEGF含量、肿瘤组织微血管密度(MVD),观察剩余小鼠生存期。结果 Es瘤内组小鼠肿瘤体积大小、VEGF及MVD表达均小于其他3组(P<0.05),Es瘤内组生存期与Es静脉组比较均较阿霉素组、对照组延长(P<0.05),但两者生存期差异无统计学意义(P>0.05)。结论 Es联合Adm在抑制血管生成与肿瘤生长方面,瘤内应用Es抑瘤效果优于静脉应用,但前者小鼠生存期的延长较后者无明显优势。
Objective To study the inhibitory effect of endostatin (Es) combined with intramuscular and tail vein administration and intraperitoneal injection of doxorubicin (Adm) on angiogenesis and tumor growth in mouse H22 hepatoma cells. Methods H22 hepatoma cells were inoculated subcutaneously in the back of 40 mice. When the tumor diameter was about 1 cm, the mice were randomly divided into 4 groups according to body weight. Control group: intraperitoneal and intraperitoneal injection of saline; Es intra-tumor group: intraperitoneal injection of Es + Injections of Adm; Es vein group: Esu injection every other day Es + intraperitoneal injection of Adm; Adm group: every other day intravenous injection of saline plus intraperitoneal injection of Adm. The diameter of subcutaneous tumor was measured every 3d, and the tumor growth curve was drawn. On the 15th day, 5 mice were sacrificed in each group. The content of VEGF and the microvessel density (MVD) in tumor tissue were measured to observe the survival of the remaining mice. Results The tumor size, the expression of VEGF and MVD in ES group were significantly lower than those in the other three groups (P <0.05). The survival time in ES group was longer than that in Es vein group and the control group (P < 0.05), but there was no significant difference in survival between the two groups (P> 0.05). Conclusion Es combined with Adm has better antitumor efficacy than intravenous administration in inhibiting the angiogenesis and tumor growth. However, the survival of mice in the former combined with Adm has no obvious advantage over the latter.