脂质体-IP10复合物对小鼠4T1乳腺癌的治疗作用  

Antitumor and Antimetastatic Activities of Plasmid pcDNA3.1IP10 Complexed with Cationic Liposome in Mice with 4T1 Breast Cancer

作　　者：唐清清[1] 石薇[1] 律慧敏[1] 彭星辰[1] 文艳君[1] 

机构地区：[1]四川大学华西医院生物治疗国家重点实验室,成都610041

出　　处：《四川大学学报（医学版）》2009年第2期195-198,共4页Journal of Sichuan University(Medical Sciences)

基　　金：国家"973"项目(No.2004CB518807)资助

摘　　要：目的用1,2-二油酰-3-三甲胺基丙烷(DOTAP)+胆固醇(CHOL)脂质体包裹pcDNA3.1-γ干扰素诱导蛋白-10(IP10)制备脂质体质粒DNA复合体即Lip-IP10,观察其对抗小鼠4T1乳腺癌的原位瘤及肺转移瘤的治疗作用,并探讨其作用机制。方法建立4T1乳腺癌模型,将36只荷瘤小鼠随机分为生理盐水(NS)组、脂质体-pcDNA3.1复合物(Lip-null)组和脂质体-IP10复合物(Lip-IP10)组,尾静脉给药,观察各组肿瘤体积、肺转移结节数及小鼠生存期。原位瘤进行CD31染色,测定微血管密度(MVD)。结果与两对照组比较,Lip-IP10组的肿瘤体积明显较小(P<0.05),肺转移结节显著减少(各组中位数为NS组45个,Lip-null组40个,Lip-IP10组3个,P<0.05),生存期延长(P<0.05),CD31染色结果显示,Lip-IP10组的肿瘤MVD值较低(NS组44.25±5.51,Lip-null组43.45±4.21,Lip-IP10组21.50±5.41,P<0.05)。结论静脉给予Lip-IP10复合体可抑制小鼠4T1乳腺癌的原位瘤及肺转移瘤,其作用机制与IP10抑制肿瘤血管生成有关。Objective To determine the antitumor and antimetastatic effects of plasmid pcDNA3. 1-IP10 complexed with cationic liposome （DOTAP ： CHOL） in mice with 4T1 breast cancer. Methods BALB/c mice model with 4T1 breast cancer was established. Thirty six mice with 4T1 breast cancers were divided randomly into three groups, which were intravenously injected with normal saline （200 μL）,Lip-null （50 /μg DNA, 200 μL） and Lip-IP10 （50μg DNA,200 μL） respectively every five days for six doses. The size of the tumors, the number of lung metastasis noduls and survival time were measured. Four mice from each group were sacrificed 43 days after tumor implantation. The tumor microvascula densities （MVD） were detected by immunohistochemical staining. Results Lip-IP10 inhibited the growth of tumor and the formation of lung metastasis neoplasm （P〈0.05）. The Lip-IP10 group had a median of 3 lung metastasis nodules, less than the NS group （45） and Lip-null group （40） （P 〈0. 05）. Lip-IP10 significantly prolonged the survival time of the tumor-bearing mice （P 〈 0. 05）. The histomorphometric analysis revealed a decreased MVD in the Lip-IP10 group （21.50±5.41 vs 44.25±5.51 for the NS group and 43.45±4.21 for the Lip-null group, P〈0.05）. Conclusion IP10 encapsulated in cationic liposome inhibits the growths and metastases of 4T1 breast cancers, which is based on the mechanism of IP10 inhibiting tumor angiogenesis.

关 键 词：γ干扰素诱导蛋白10 阳离子脂质体 乳腺癌 基因治疗 

分 类 号：R737.9[医药卫生—肿瘤]