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目的研究羟基红花黄色素A(HSYA)对小鼠Lewis肺癌移植瘤中微血管密度(MVD)及血管内皮生长因子(VEGF)mRNA表达的影响,探讨HSYA抑制肿瘤的分子机制。方法运用C57/BL小鼠接种Lewis肺癌细胞株于右侧肋腹皮下建立小鼠肺癌移植瘤模型,随机分为对照组(生理盐水)、环磷酰胺组(CTX)、HSYA不同剂量组(28 mg/L、56 mg/L、112 mg/L),给药方式均为腹腔注射给药。用药22 d后脱颈处死小鼠并剥离肿瘤组织,采用免疫组织化学法检测MVD,采用实时荧光定量PCR检测各组肿瘤组织中VEGF mRNA的表达情况。结果 56 mg/L、28 mg/L HSYA组与CTX组小鼠肿瘤组织MVD分别为30.01±3.12、22.56±2.11、16.21±2.40,显著低于对照组的41.10±2.93以及112 mg/L HSYA组的37.66±3.04,差异有统计学意义(X~2=2.82,P=0.010;X~2=3.16,P=0.007;X~2=4.58,P=0.000)及(X~2=1.98,P=0.038;X~2=2.45,P=0.016;X~2=3.82,P=0.001)。28 mg/L HSYA组与对照组VEGF扩增荧光表达阈值所需循环次数比较,差异无统计学意义,但其VEGF mRNA的表达值仅为0.43±0.16,明显低于对照组的0.82±0.06,差异有统计学意义(F=0.77,P=0.038)。结论 28 mg/L HSYA能够使小鼠Lewis肺癌移植中MVD明显减少,具有抑制肿瘤生长的作用,可能与下调VEGF mRNA表达有关。
Objective To study the effect of hydroxysafflor yellow A (HSYA) on the microvessel density (MVD) and the expression of vascular endothelial growth factor (VEGF) mRNA in Lewis lung carcinoma in mice and to explore the molecular mechanism of HSYA inhibiting tumor. Methods The Lewis lung carcinoma cell line was inoculated subcutaneously in C57 / BL mice to establish a mouse lung cancer xenograft model. The model mice were randomly divided into control group (NS), cyclophosphamide group (CTX), HSYA group (28 mg / L, 56 mg / L, 112 mg / L) were administered intraperitoneally. Twenty-two days after treatment, the mice were killed by atrophy and the tumor tissue was removed. The MVD was detected by immunohistochemical method. The expression of VEGF mRNA in tumor tissues was detected by real-time fluorescence quantitative PCR. Results The MVD of 56 mg / L, 28 mg / L HSYA and CTX groups were 30.01 ± 3.12, 22.56 ± 2.11 and 16.21 ± 2.40, respectively, which were significantly lower than those of control group 41.10 ± 2.93 and 112 mg / L HSYA group (P = 0.010; X ~ 2 = 3.16, P = 0.007; X ~ 2 = 4.58, P = 0.000) and (X ~ 2 = 1.98, P = 0.038; X ~ 2 = 2.45, P = 0.016; X ~ 2 = 3.82, P = 0.001). There was no significant difference in the number of cycles required for fluorescence amplification of VEGF between the 28 mg / L HSYA group and the control group, but the expression of VEGF mRNA was only 0.43 ± 0.16, significantly lower than that of the control group (0.82 ± 0.06) The difference was statistically significant (F = 0.77, P = 0.038). Conclusion 28 mg / L HSYA can significantly reduce the MVD in mice with Lewis lung carcinoma and inhibit tumor growth, which may be related to the down-regulation of VEGF mRNA expression.