摘要
目的 研究小分子三肽CMS0 2 4对人肝癌裸鼠转移模型肿瘤生长和转移的抑制作用。方法 将高转移性人肝癌细胞株HCCLM6接种于裸小鼠皮下 ,成瘤后移植于 2 0只裸鼠肝脏 ,制成原位移植自发性多向转移肝癌模型 ,随机分为治疗组和对照组 ,各 10只。治疗组按 30 0 μg/kg剂量腹腔内注射CMS0 2 4 0 .1ml,对照组注射等体积的 0 .85 %氯化钠注射液。每日 1次 ,共治疗 35d。观察荷瘤裸鼠的体重变化、腹腔内转移和肺转移的发生率和转移灶的数目 ,并测量血液学和血液生化指标。结果 至观察期 35d时 ,治疗组 10只裸鼠全部存活 ,对照组存活 9只。治疗组肿瘤的平均重量1.9g± 0 .5g ,对照组 2 .3g± 0 .8g ,差异无显著意义。腹壁转移和腹腔内转移的发生率对照组均为10 0 % ,而治疗组则分别为 6 0 %和 5 0 % (P <0 .0 5 ) ;血性腹水和肝内肉眼可见转移结节的发生率对照组分别是 70 %和 90 % ,治疗组分别是 2 0 %和 4 0 % (P >0 .0 5 )。Ⅰ、Ⅱ、Ⅲ、Ⅳ级肺转移灶的中位数对照组分别是 92、2 4、15、16个 ,治疗组分别是 2 4、2 0、10、8个 ,两组Ⅰ级肺转移灶差异有显著意义(P <0 .0 5 )。两组裸鼠的体重变化、外周血常规指标和血生化指标的差异均无显著意义。未观察到与药物相关的毒副作用。结论 小分子三肽CMS0 2 4对?
OBJECTIVE THIS EXPERIMENT WAS DESIGNED TO STUDY THE EFFECT OF SMALL MOLECULE TRIPEPTIDE CMS024 ON TUMOR GROWTH AND METASTASIS IN A NUDE MICE MODEL OF HUMAN HEPATOCELLULAR CARCINOMA (HCC) METASTASIS. METHODS HIGHLY METASTATIC HUMAN HCC CELL STRAIN HCCLM6 WAS INJECTED INTO SUBCUTANEOUS REGION OF NUDE MICE. WHEN THE SUBCUTANEOUS TUMOR REACHED 0.8 CM IN DIAMETER, THE TUMOR WAS REMOVED AND CUT INTO SMALL PIECES ABOUT 1 MM IN DIAMETER AND IMPLANTED ORTHOTOPICALLY INTO THE LIVER OF 20 BALB/C NUDE MICE, WHICH WERE RANDOMIZED INTO TREATMENT GROUP AND CONTROL GROUP EACH WITH 10 MICE. THE TREATMENT GROUP RECEIVED DAILY CMS024 INTRAPERITONEAL INJECTION AT THE DOSE OF 300 ΜG/KG BEGINNING FROM THE SECOND POSTOPERATIVEDAY. THE CONTROL GROUP RECEIVED INTRAPERITONEAL INJECTION OF EQUAL AMOUNT OF 0.85% SODIUM CHLORIDE SOLUTION. THE MICE WERE OBSERVED FOR SIGNS OF DISEASE DEVELOPMENT. THIRTY-FIVE DAYS LATER, THE MICE WERE SACRIFICED AND ABDOMINAL AND PULMONARY METASTASES WERE RECORDED AND PERIPHERAL BLOOD HEMATOLOGICAL AND BIOCHEMICAL PARAMETERS WERE DETERMINED. RESULTS AFTER 35 DAYS OF INTERVENTION, ALL THE 10 MICE IN THE TREATMENT GROUP WERE ALIVE AND WELL, BUT THERE WERE ONLY 9 LIVING MICE IN THE CONTROL GROUP. THE MEAN TUMOR WEIGHTS WERE 1.9 G±0.5 G IN THE TREATMENT GROUP AND 2.3 G±0.8 G IN THE CONTROL GROUP (P>0.05). THE ABDOMINAL WALL METASTASES AND INTRAPERITONEAL METASTASES WERE 100% FOR THE CONTROL GROUP AND ONLY 60% AND 50%, RESPECTIVELY, FOR THE TREATMENT GROUP (P<0.05). BLOODY ASCITES AND GROSS INTRAHEPATIC METASTATIC NODULES WERE FOUND IN 70% AND 90% OF NUDE MICE, RESPECTIVELY,FOR THE CONTROL GROUP, AND 20% AND 40%, RESPECTIVELY, FOR THE TREATMENT GROUP (P>0.05). THE MEDIAN NUMBER OF GRADESⅠ, Ⅱ, Ⅲ AND Ⅳ PULMONARY METASTASES WERE 92, 24, 15 AND 16, RESPECTIVELY, FOR THE CONTROL GROUP, AND 24, 20, 10 AND 8, RESPECTIVELY, FOR THE TREATMENT GROUP. THERE WERE STATISTICALLY SIGNIFICANT DIFFERENCES IN THE NUMBER OF GRADE Ⅰ PULMONARY METASTASES BETWEEN THE TREATMENT GROUP AND THE CONTROL GROUP ( 24 VS 92, P<0.05). NO STATISTICALLY SIGNIFICANT DIFFERENCES IN THE BODY WEIGHT, PERIPHERAL BLOOD HEMATOLOGICAL AND BIOCHEMICAL PARAMETERS WERE OBSERVED BETWEEN THE TWO GROUPS. NO TOXIC EFFECTS WERE OBSERVED DURING THE OBSERVATION PERIOD. CONCLUSIONS SMALL MOLECULE TRIPEPTIDE CMS024 DEMONSTRATED POSITIVE EFFECTS TO RETARD TUMOR GROWTH AND INHIBIT LOCO-REGIONAL AND LONG DISTANCE METASTASES IN A NUDE MICE MODEL OF HUMAN HCC METASTASIS, AND NO OBVIOUS TOXIC OR SIDE EFFECTS ON THE TUMOR BEARING NUDE MICE.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2004年第8期675-679,共5页
National Medical Journal of China
基金
国家自然科学基金资助项目 (3 0 10 0 0 77)
上海市科技发展基金资助项目 (0 3QD14 0 0 8)
高等学校全国优秀博士学位论文作者专项资金资助项目 (2 0 0 2 63 )
关键词
肝癌
肿瘤转移
动物模型
小分子肽
血清学指标
PEPTIDES
CARCINOMA,HEPATOCELLULAR
NEOPLASM,METASTASIS
MODELS,ANIMAL
