摘要：
Objective To observe the inhibitory effect on lymph node metastasis of pancreatic cancer and lymphangiogenesis in mice by injection of KAll gene within xenograft tumor.Methods Pancreatic cancer cell line MiaPaCa-2 wag used to construct the nude mice models bearing tumors,then the mice were divided into normal saline group,Ad group and Ad-KAI1 group.Since the successful model construction,normal saline,Ad,Ad-KAI1 was injected every week for 3 times,respectively in the three groups,then the tumor size was documented.50 d after model construction,the tumor and enlarged lymph nodes were collected and subjected to pathological exam,and the expression of LYVE-1 and the MLVD in xenograft tumor was detected by immunohistochemistry.Results Two weeks after MiaPaCa-2 implantation,the model was 100％ successfully constructed.The growth curve of subcutaneous tumor among 3 groups was not statistically significant (P＞0.05) ; the weights of subcutaneous tumor in the 3 groups were (2514.4 ±351.3),(2466.1 ± 295.5),(2294.4±255.4) mg after 50 d,and the difference among the 3 groups was not statistically significant (P ＞0.05).Enlarged lymph nodes metastasis was observed in 8 mice (80％) in normal saline group,and 20 lymph nodes were collected,with 2.0 lymph nodes per mice; and enlarged lymph nodes metastasis was observed in 7 mice (70％) in Ad group,and 15 lymph nodes were collected,with 1.5 lymph nodes per mice; while enlarged lymph nodes metastasis was observed in 4 mice (40％) in Ad-KAI1 group,and 6 lymph nodes were collected,with 0.6 lymph nodes per mice.All the lymph nodes were confirmed to be metastasis of the primary tumor after pathologic exam.The difference of lymph nodes metastasis,number of lymph nodes metastasis per mice among the 3 groups was statistically significant (F =3.14,3.35,P ＜ 0.05).The MLVD of subcutaneous tumor among the 3 groups was (18.70 ± 5.60),(19.40 ± 4.58),(9.80 ±4.10)/400 times magnification,the MLVD of Ad-KAI1 group was significantly lower than those in normal saline group and Ad group (F10.76,11.36,P ＜ 0.05),but the difference between normal saline group and Ad group was not statistically significant.Conclusions KAI1 can inhibit the lymph node metastasis of pancreatic cancer,and the mechanism may be related with decreased lymphangiogenesis and reduced lymphatic vessel density.%目的 探讨KAI1基因对裸鼠胰腺癌种植瘤淋巴结转移及淋巴管新生的作用.方法 建立裸鼠的人胰腺癌MiaPaCa-2细胞皮下种植瘤模型,成瘤后应用KAI1腺病毒(Ad-KAI1)瘤内注射治疗,每周1次,共3次,以瘤内注射腺病毒(Ad)或生理盐水组作为对照,记录肿瘤生长情况.成瘤50 d收集瘤体及肿大淋巴结,常规病理学检查,并采用免疫组化法检测瘤组织中淋巴管特异性标志物LYVE-1表达,计算微淋巴管密度(MLVD).结果 裸鼠接种MiaPaCa-2细胞2周后100％成瘤.生理盐水组、Ad组、Ad-KAI1组裸鼠种植瘤的生长速度无明显差异(P＞0.05);50 d后收集的瘤体重量分别为(2514.4 ±351.3)、(2466.1±295.5)、(2294.4±255.4) mg,组间差异无统计学意义.生理盐水组8只(80％)发现肿大淋巴结转移,共收集到肿大淋巴结20枚,平均2.0枚/只;Ad组7只(70％)发现肿大淋巴结,共收集到肿大淋巴结15枚,平均1.5枚/只;Ad-KAI1组4只(40％)发现肿大淋巴结,共收集到肿大淋巴结6枚,平均0.6枚/只.所有肿大淋巴结均经病理学检查确定为肿瘤的淋巴转移灶.3组裸鼠肿瘤淋巴结转移及每只裸鼠平均淋巴结转移数的差异均有统计学意义(F值分别为3.14、3.35,P值均＜0.05).生理盐水组、Ad组、Ad-KAI1组裸鼠胰腺癌种植瘤组织中MLVD分别为(18.70±5.60)、(19.40±4.58)、(9.80±4.10)个/400倍视野,Ad-KAI1组MLVD显著低于生理盐水组和Ad组,差异有统计学意义(F值分别为10.76、11.36,P值均＜0.05),而生理盐水组和Ad组间的差异无统计学意义.结论 KAI1可能通过减少裸鼠种植瘤组织中的淋巴管新生、降低微淋巴管密度来抑制胰腺癌的淋巴转移.
