苹果酸舒尼替尼对LA795肺腺癌小鼠移植瘤生长凋亡的影响

Effects of SU11248 on Growth and Apoptosis of Lung Adenocarcinoma LA795 in Mice

目的:探讨苹果酸舒尼替尼(SU11248)对LA795肺腺癌小鼠移植瘤生长凋亡的影响。方法:复制肺腺癌LA795细胞的T739小鼠移植瘤模型,将50只接种高转移性LA795肺腺癌细胞T739雄性小鼠随机分成对照组、阴性治疗组、低剂量SU11248组、中剂量SU11248组、高剂量SU11248组。接种4d后开始用SU11248干预,每5d用游标卡尺测量皮下移植瘤最大长径(a)和横径(b),计算肿瘤体积,平均瘤体积=a×b^2/2,计算肿瘤生长抑制率。接种24d后脱颈臼处死全部小鼠,解剖剥离皮下移植瘤固定,采用免疫组化和TUNEL法检测增殖细胞核抗原(PCNA)的表达和肿瘤细胞凋亡,计数增殖指数和凋亡率。结果:各剂量组移植瘤生长明显慢于对照组与阴性对照组,以高剂量级生长最慢;生长抑制率明显高于对照组与阴性对照组,以高剂器组生长最高,差异有显著性。各剂量组增殖指数低于对照组和阴性对照组,低剂量组差异无显著性,中剂量组和高剂量组差异有显著性;各剂量组间增殖指数与剂量呈反向变化,剂量越大,SPF越低,差异有显著性。各剂量组肿瘤细胞凋亡率高于对照组和阴性对照组,低剂量组差异无显著性,中剂量组和高剂量组差异有显著性;各剂量组间肿瘤细胞凋亡率与剂量呈同向变化,剂量越大,肿瘤细胞AR越大,差异有显著性。结论:SU11248可能具有抑制肺腺癌肿瘤细胞生长和促进肿瘤细胞的凋亡作用。

Objective：To observe the influence of growth and apoptosis of SU11248 to LA795 lung adenocareinoma tumor in mice. Methods：Duplicate adenocarcinoma of lung LA795 cell＇s T739 mouse transplant lump models.And 50 vaccinated high transferability LA795 adenoearcinoma of lung cell T739 male mouse were randomly divided into the control group,the negative treatment group,the low dose SUl1248 group,the average dosage SU 11248 group,and the high dose SU11248 group.After vaccinated for 4 days,drugs were applied to intervention.During the medication period,side-effects were observated,and hypodermic transplant lump biggest major axis（a）and transverse diameter（b）were surveyed with Vernier caliper every 5 days,and then calculated tumor volume,average lump volume=a× b^2/2,and also calculated tumor growth suppression rate.After vaccinated for 24 days,total mouse were executed through escapes the neck mortar, dissected peeling hypodermic transplant lump and weighed,dissection fixed stripping nude,and immunohistochemistry and TUNEL assay were applied to examine proliferating cell nuclear antigen（PCNA）expression and tumor cell apoptosis,then proliferation index and apoptosis rate were counted.Results：The control group and the negative control group transplant the lump grew obviously quicker than in various monitoring teams,but the high monitoring team grew slower.Growth inhibition rate of the highest growth of high-dose group was significantly higher than that of the negative control group,there was a significant difference.Proliferation index of the dose group the control group and negative control group were than those of other groups,and there was no significant difference in low-dose group,but there was a significant difference in the dose group and high dose group,Between various monitoring teams,tumor cell apoptosis rate and the dosage assumed the synchronism change,the dosage bigger, tumor cell apoptosis rate bigger, and the difference was significant.The rate of apoptosis of tumor cells of each dose group was higher than that of negative control group,there was no significant difference in low- dose group,but there was a significant difference in the dose group and high dose group.The rate of apoptosis of tumor cells of all dose groups showed the same dose to change,the greater the dose,the greater the AR tumor ceils,there was a significant difference.Conclusions： SU 11248 may have inhibited the growth of lung adenocarcinoma tumor cells and promote apoptosis of tumor cells.