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乳岩宁方联合依西美坦对乳腺癌荷瘤裸鼠 JNK/MAPK信号通路的影响*(PDF)

《云南中医学院学报》[ISSN:1000-2723/CN:53-1048/R]

期数:
2018年04期
页码:
7-12
栏目:
实验研究
出版日期:
2019-03-25

文章信息/Info

Title:
Effect of Ruyanning Decotion Combined with Exemestane on JNK/MAPK Signaling Pathway in Breast Cancer Bearing Nude Mice
文章编号:
1000 - 2723(2018)04 - 0007 - 06
作者:
邢向荣1高宏2殷东风2△
(1. 辽宁中医药大学,辽宁 沈阳 110032;2. 辽宁中医药大学附属医院肿瘤科,辽宁 沈阳 110032)
Author(s):
XING Xiangrong1 GAO Hong2 YIN Dongfeng2
(1. Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China;2. Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China)
关键词:
乳岩宁方 依西美坦 JNK/MAPK信号通路
Keywords:
Ruyanning Decoction exemestane JNK/MAPK signaling pathway
分类号:
R285.5
DOI:
10.19288/j.cnki.issn.1000-2723.2018.04.002
文献标识码:
A
摘要:
目的观察乳岩宁方联合依西美坦对MDA-MB-435乳腺癌细胞荷瘤裸鼠JNK/MAPK信号通路相关蛋白表达的影响,探讨乳岩宁方联合依西美坦治疗绝经后难治性(HER-2/neu高表达)乳腺癌的作用机制。方法造MDA-MB-435乳腺癌细胞荷瘤去势裸鼠移植模型,分为4组:空白对照组、乳岩宁方组、依西美坦组、联合组(乳岩宁方+依西美坦),分别每日1次灌胃给药,21 d后处死裸鼠,取材瘤体。采用Western blot及RT-PCR法检测瘤组织中JNK/MAPK信号通路JNK蛋白及其下游相关蛋白STAT3、Bcl-2、p53、caspase8的表达。结果乳岩宁方组、依西美坦组、联合组的抑瘤率分别为37.53%、60.83%、66.09%。与空白对照组相比,乳岩宁方组、依西美坦组和联合组的JNK、STAT3、Bcl-2的蛋白表达均明显下降,有统计学意义(P<0.05)。其中JNK蛋白的表达,联合组较乳岩宁方组、依西美坦组明显下降,有统计学意义(P<0.05);STAT3蛋白的表达,乳岩宁方组较依西美坦组和联合组明显下降,有统计学意义(P<0.05);Bcl-2蛋白的表达乳岩宁方组、依西美坦组、联合组之间无统计学意义(P>0.05)。与空白对照组相比,乳岩宁方组、依西美坦组和联合组p53、Caspase8的基因表达均明显升高,有统计学意义(P<0.05)。联合组p53、Caspase8的基因表达较乳岩宁方组、依西美坦组明显升高,有统计学意义(P<0.05)。结论乳岩宁方联合依西美坦可能对JNK/MAPK信号通路有双向调节作用,一方面下调JNK蛋白表达及其下游蛋白STAT3、Bcl-2表达起到抑制乳腺癌细胞增殖的作用;另一面能上调p53、Caspase8基因表达,起到促进乳腺癌细胞凋亡的作用,最终起到抗肿瘤的作用。中药复方联合内分泌治疗将成为激素受体阳性乳腺癌在后芳香化酶抑制剂时代(AI+)治疗的新模式。
Abstract:
Objective To observe the effect of Ruyanning Decotion combined with exemestane on the expression of JNK/MAPK signaling pathway related protein in MDA-MB-435 breast cancer cells bearing nude mice. To explore the mechanism of Ruyanning Decotion combined with exemestane in the treatment of postmenopausal refractory(HER-2/neu high expression) breast cancer. Methods Created MDA-MB-435 breast cancer cells in tumor bearing nude mouse transplantation model, divided into 4 groups:control group, Ruyanning Decoction group, exemestane group and combination group(Ruyanning Decoction+exemestane), respectively, once a day by gavage, 21 days after the mice were killed, tumors were. Western blot and RT-PCR were used to detect the expression of JNK/MAPK signaling pathway JNK protein and its downstream related proteins STAT3, Bcl-2, P53 and caspase8 in tumor tissues. Results The inhibition rate of Ruyanning Decoction group, exemestane group and combination group were 37.53%, 60.83%, and 66.09%, respectively. Compared with the control group, Ruyanning Decoction group, exemestane group and combined group of JNK, STAT3 and Bcl-2 protein expression were significantly decreased, with statistical significance(P<0.05). The expression of JNK protein in the combined group was significantly lower than that in Ruyanning Decoction group and exemestane group(P<0.05), and the expression of STAT3 protein in Ruyanning Decoction group was significantly lower than that of the exemestane group and the combined group(P<0.05), and the expression of Bcl-2 protein in the Ruyanning Decoction group, the exemestane group and the combined group, there was no statistical significance between the three groups(P>0.05). Compared with the control group, Ruyanning Decoction group, exemestane group and combination group of p53 and Caspase8 gene expression were significantly increased, with statistical significance(P<0.05). The gene expression of p53 and Caspase8 in combined group was significantly higher than that in Ruyanning Decoction group and exemestane group, with statistical significance(P<0.05). Conclusion Ruyanning Decoction combined with exemestane may have a bidirectional regulation effect on JNK/MAPK signaling pathway. On the one hand, the expression of JNK protein and its downstream protein STAT3 and Bcl-2 can inhibit the proliferation of breast cancer cells. The other side can up regulate the expression of p53 and Caspase8 genes, and play a role in promoting apoptosis of breast cancer cells, and finally play an anti-tumor effect. Combination of Chinese herbal medicine and endocrine therapy will become a new mode of treatment for hormone receptor positive breast cancer in the era of AI+.

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备注/Memo

备注/Memo:
收稿日期: 2018 - 08- 18
*基金项目: 辽宁省科学技术计划项目(2013226012)
第一作者简介: 邢向荣(1979-),女,副主任医师,在读博士研究生,研究方向:肿瘤的中西医结合治疗。
△通信作者: 殷东风,E-mail:lnzy_oncology@aliyun.com
更新日期/Last Update: 2018-10-30