苏拉明对肺腺癌小鼠移植瘤生长的影响及其机制

背景与目的:有研究表明,苏拉明对恶性肿瘤有明显抑制作用,但有关其对肺腺癌体内抗瘤作用的报道很少。本实验观察苏拉明对肺腺癌LA795细胞的T739小鼠移植瘤生长和转移的抑制作用,并探讨其作用机制。方法:将32只接种LA795肺腺癌细胞T739的小鼠随机分成4组:对照组、顺铂组、苏拉明组、联合组(苏拉明加顺铂组),每组8只。用药16d,观察肿瘤生长情况,于接种后24d处死各组小鼠,取出双肺并剥离皮下肿瘤,计算出肺转移发生率,计数各组小鼠肺表面转移结节数并算出肺表面结节转移抑制率;收集移植瘤标本,称重和测量体积,免疫组化和图像分析系统定量检测肿瘤组织中表皮生长因子受体(epidermal growth factor receptor,EGFR)、P-选择素和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达。结果:顺铂组、苏拉明组、联合组肿瘤的生长明显受到抑制,瘤重明显低于对照组,其抑瘤率分别为34.9%、23.8%、57.3%;苏拉明组及联合组与对照组和顺铂组相比肺转移发生率、肺表面转移结节数明显下降(P<0.05),而顺铂组与对照组比较差异则无统计学意义。EGFR和P-选择素的表达对照组高于顺铂组、苏拉明组、联合组,对照组、顺铂组、苏拉明组、联合组EGFR表达的灰度值分别为157.7±6.1、130.7±5.9、110.3±5.8、89.2±5.4,P-选择素表达的灰度值分别为134.5±5.7、117.9±5.1、96.2±5.4、78.3±4.5,各用药组与对照组相比差异均有统计学意义(P<0.05或P<0.01);对照组、顺铂组、苏拉明组、联合组增殖指数(S phase fraction,SPF)分别为(89.7±3.8)%、(68.8±4.0)%、(65.2±4.2)%、(51.3±4.2)%,各用药组SPF都比对照组低,差异有统计学意义(P<0.01)。结论:苏拉明可明显抑制肺腺癌细胞在小鼠体内的生长和转移,其作用机制可能为通过调控肿瘤细胞中的EGFR和P-选择素表达,从而抑制肿瘤细胞增殖和减少肿瘤细胞的粘附而防止转移。

Inhibitory effects of suramin on growth of transplanted lung adencarcinoma in mice and its mechanisms

BACKGROUND & OBJECTIVE: Recent study found that suramin could inhibit the growth of malignant tumors, but its in vivo effect on lung adenocarcinoma has seldom been reported. This study was to investigate the inhibitory effects of suramin on the growth and metastasis of transplanted lung adenocarcinoma in mice, and explore the mechanisms. METHODS: Lung adenocarcinoma LA795 cells were transplanted into 32 T739 mice. The tumor-bearing mice were randomized into control group, cisplatin (DDP) group, suramin group, and combination (suramin plus DDP) group? each group contained 8 mice. Different treatments were served since Day 4 after transplantation. All mice were killed 24 days after transplantation. The metastatic tumor foci on the lung in mice were counted. The occurrence rate of lung metastasis and the inhibition rate of metastatic foci were calculated. The volume and weight of tumors were measured. The expression of epidermal growth factor receptor (EGFR), P-selectin and proliferating cell nuclear antigen (PCNA) in tumor tissues were detected by immunhistochemistry. RESULTS: DDP and suramin used alone or in combination significantly inhibited the growth of LA795 cells in mice (P<0.05), with growth inhibition rates of 34.9%, 23.8% and 57.3%, respectively. The occurrence rate of lung metastasis and the number of metastatic foci on lung surface were significantly lower in suramin group and combination group than in DDP group and control group (P<0.05). The protein levels of EGFR and P-selectin were significantly higher in control group than in DDP group, suramin group, and combination group (157.7+/-6.1 vs. 130.7+/-5.9, 110.3+/-5.8, and 89.2+/-5.4, P<0.05? 134.5+/-5.7 vs. 117.9+/-5.1, 96.2+/-5.4, and 78.3+/-4.5, P<0.01). The S phase fraction of tumor cells was significantly higher in control group than in DDP group, suramin group, and combination group (89.7+/-3.8)% vs. (68.8+/-4.0)%, (65.2+/-4.2)%, and (51.3+/-4.2)%, P<0.01)]. CONCLUSION: Suramin could inhibit the proliferation and metastasis of LA795 cells in T739 mice through regulating the expression of EGFR, P-selectin and PCNA.