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目的:研究丝裂原活化蛋白激酶(MAPK/ERK)信号通路抑制剂(PD98059)对ER阳性表达的Ishikawa和ER低表达的HEC-1A人子宫内膜癌细胞系的裸鼠体内抗增殖作用,探讨阻断MAPK/ERK信号传导通路治疗子宫内膜癌的可行性。方法:体外培养人子宫内膜癌Ishikawa、HEC-1A细胞,将对数生长期的两种细胞分别接种于裸鼠背部皮下,建立子宫内膜癌裸鼠移植瘤模型。将两种细胞系成瘤阳性裸鼠随机分为对照组和实验组,每组6只,分别腹腔注射生理盐水和PD98059,每周2次,共3周,观察各组裸鼠移植瘤的生长情况,建立移植瘤生长曲线,计算抑瘤率。实验结束时取肿瘤组织切片HE染色,原位末端标记(TUNEL)法检测组织细胞的凋亡,Western blot检测各组织中ERK1/2的活化。结果:(1)PD98059能有效抑制人子宫内膜癌Ishikawa、HEC-1A细胞裸鼠皮下移植瘤的生长;(2)HE染色可见实验组瘤细胞核浆比相对较小,血管密度降低;TUNEL染色可见两种细胞移植瘤中实验组细胞凋亡率较对照组明显增加;(3)Western blot检测结果:PD98059能有效降低裸鼠移植瘤组织中p-ERK表达。结论:PD98059通过阻断MAPK/ERK信号传导通路增加Ishikawa和HEC-1A细胞裸鼠移植瘤组织中细胞凋亡,抑制肿瘤生长,抗肿瘤效果明显,可成为治疗子宫内膜癌的有效方法。
AIM: To investigate the antiproliferative effects of mitogen-activated protein kinase (MAPK / ERK) signaling pathway inhibitor (PD98059) on Ishikawa with ER expression and HEC-1A human endometrial carcinoma cell line with low ER expression in vivo. To investigate the feasibility of blocking MAPK / ERK signaling pathway in the treatment of endometrial cancer. Methods: Ishikawa and HEC-1A cells were cultured in vitro. Two kinds of cells in logarithmic growth phase were inoculated subcutaneously on the back of nude mice respectively to establish a model of xenografted endometrial carcinoma in nude mice. The tumor-positive nude mice in both cell lines were randomly divided into control group and experimental group, with 6 mice in each group. Normal saline and PD98059 were intraperitoneally injected twice a week for 3 weeks. The growth of nude mice xenografts Situation, the establishment of xenograft growth curve, calculate the inhibition rate. At the end of the experiment, the sections of the tumor were stained with HE, the apoptosis of the cells was detected by TUNEL, and the activation of ERK1 / 2 was detected by Western blot. Results: (1) PD98059 could effectively inhibit the growth of subcutaneously transplanted tumor in Ishikawa and HEC-1A cells in nude mice with endometrial carcinoma; (2) HE staining showed that the cytoplasm of tumor cells in the experimental group was relatively smaller and the blood vessel density was lower; TUNEL staining It can be seen that the apoptotic rates of the experimental groups in the two cell xenografts were significantly higher than those in the control group. (3) Western blot results showed that PD98059 could effectively reduce the expression of p-ERK in the transplanted xenografts in nude mice. CONCLUSION: PD98059 can increase the apoptosis of Ishikawa and HEC-1A cells in nude mice by blocking the MAPK / ERK signal transduction pathway, inhibit the growth of the tumor and have obvious anti-tumor effect, which can be an effective method for the treatment of endometrial cancer.