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目的:探讨雷帕霉素对胰腺癌体内生长的抑制作用及其对基质细胞衍生因子1α(SDF-1α)的影响。方法:20只裸鼠胰腺注射胰腺癌SW1990细胞悬液后,随机均分为实验组与对照组,实验组裸鼠每日雷帕霉素(1.5mg/kg)腹腔注射,对照组以同样的方式给予等体积溶剂。3周后取移植瘤,比较两组肿瘤的生长情况,免疫组化法检测肿瘤组织单核-巨噬细胞、肿瘤相关巨噬细胞(TAM)浸润情况及p-m TOR、HIF-1α、SDF-1α蛋白的表达;Westonblot及q RT-PCR法检测肿瘤组织p-m TOR、HIF-1α、SDF-1α的蛋白与m RNA表达。结果:与对照组比较,实验组的肿瘤重量(0.3340g vs.1.7790g)与体积(0.2375mm3 vs.1.2662mm~3)均明显减小(均P<0.05)。免疫组化结果显示,与对照组比较,实验组肿瘤组织浸润的单核-巨噬细胞、TAM计数均明显少(均P<0.05);p-m TOR、HIF-1α、SDF-1α蛋白表达率均明显降低(均P<0.05);肿瘤组织SDF-1α表达评分与TAM计数呈正相关(r=0.52,P<0.05)。Westonblot与q RT-PCR结果显示,实验组肿瘤组织p-m TOR、HIF-1α、SDF-1α的蛋白与m RNA表达均低于对照组,除HIF-1αm RNA外(P>0.05),其余差异均有统计学意义(均P<0.05)。结论:雷帕霉素能抑制胰腺癌的体内生长,其机制可能与抑制m TOR通路活性而下调SDF-1α蛋白表达,进而减少肿瘤微环境中的TAM有关。
Objective: To investigate the inhibitory effect of rapamycin on pancreatic cancer in vivo and its effect on stromal cell-derived factor 1α (SDF-1α). Methods: Twenty (20) nude mice were inoculated with pancreatic cancer cell line SW1990 and randomly divided into experimental group and control group. The nude mice in experimental group were injected intraperitoneally with rapamycin (1.5mg / kg) daily. The control group received the same Way to give an equal volume of solvent. Three weeks later, the tumor was harvested and the growth of the tumors was compared. The infiltration of mononuclear macrophages and tumor-associated macrophages (TAMs) and the expressions of pm TOR, HIF-1α, SDF-1α Western blot and q RT-PCR were used to detect the protein and mRNA expression of pm TOR, HIF-1α and SDF-1α in tumor tissues. Results: Compared with the control group, the tumor weight (0.3340g vs 1.7790g) and volume (0.2375mm3 vs.1.2662mm ~ 3) of the experimental group were significantly decreased (all P <0.05). Immunohistochemistry results showed that compared with the control group, the number of TAM in infiltrating mononuclear macrophages in the experimental group was significantly lower (all P <0.05). The protein expressions of pm TOR, HIF-1α and SDF-1α (All P <0.05). The expression of SDF-1α in tumor tissue was positively correlated with TAM count (r = 0.52, P <0.05). The results of Weston blot and q RT-PCR showed that the expressions of pm TOR, HIF-1α and SDF-1α in experimental group were lower than those in control group, except HIF-1αm RNA (P> 0.05) There was statistical significance (all P <0.05). Conclusion: Rapamycin can inhibit the growth of pancreatic cancer in vivo. The mechanism may be related to inhibiting the activity of mTOR pathway and down-regulating the expression of SDF-1α protein, thereby reducing TAM in tumor microenvironment.