目的 探讨木鳖子单体化合物对羟基桂皮醛(p-hydroxycinnamaldehyde,PHD)对黑素瘤B16细胞体内生长的抑制作用。方法 应用MTS法检测PHD对B16细胞增殖的影响,倒置相差显微镜下观察形态变化。构建黑素瘤B16细胞小鼠皮下移植瘤模型,分为2组:治疗组小鼠ip 2 mg/kg PHD,模型组注射相同体积的生理盐水。观察2组小鼠成瘤情况,并测量肿瘤体积和质量;免疫组织化学法检测肿瘤组织中酪氨酸酶(Tyr)、S-100B、MMP-9、p-P38和p-ERK蛋白的表达变化;苏木精-伊红染色法(HE)分析小鼠肝和肺组织的形态学变化。结果 PHD对黑素瘤B16细胞具有明显的生长抑制作用(P<0.01)。20 μmol/L PHD处理B16细胞48 h后,细胞数量减少,呈典型分化形态。PHD治疗组的肿瘤体积和质量均明显低于模型组(P<0.01)。与模型组相比,治疗组小鼠肿瘤组织中Tyr和p-P38蛋白的表达水平升高,MMP-9、S-100B和p-ERK蛋白表达水平则明显降低。治疗组小鼠肝和肺无明显组织形态学改变,模型组小鼠肺部有肿瘤转移。结论 PHD对小鼠体内黑素移植瘤的生长具有显著抑制作用。

Objective To investigate the inhibitory effect of p-hydroxylcinnamaldehyde (PHD) from Momordicae Semen seeds on growth of mouse melanoma B16 cells in vivo. Methods The inhibitory effect of PHD on growth of mouse melanoma B16 cells was measured by MTS method. Morphological changes of B16 cells were observed by phase contrast microscope. The xenograft tumor models of B16 cells in mice were established and divided into two groups:The mice in treatment group were treated with PHD (2 mg/kg) and in control group (treated with equal volume of normal saline). The growth of xenograft tumors in mice was observed and their sizes and weights were measured. The expression of Tyr, MMP-9, S-100B, p-P38, and p-ERK in tumor tissues was detected by immunohistochemical method. Morphological changes of lung and liver tissues in mice were observed by HE staining. Results PHD had obvious inhibitory effect on the growth of B16 cells in vitro (P<0.01). The morphological changes of B16 cells were typically differentiated after treated with 20 μmol/L PHD for 48 h. The average volume and weight of tumor tissues in mice of PHD treatment group were significantly decreased as compared with those of the control group (P<0.01). Compared to the control group, the expression levels of Tyr and p-P38 in PHD treatment group were increased (P<0.05), while the expression levels ofMMP-9, S-100B, and p-ERK were decreased (P<0.05). No obvious morphological changes were found in liver and lung tissues of mice in PHD treatment group and the control group. However, lung tumor metastasis was found in control group mice. Conclusion PHD has inhibitory effect on the growth of xenograft tumor of mouse melanoma cells in mice.

河北省自然科学基金项目(H2015206376);河北省医学科学研究重点课题计划项目(20120120)