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肠苓膏对裸鼠移植性结直肠癌增殖及肝转移的抑制作用。

Inhibitory effects of Chanling Gao on the proliferation and liver metastasis of transplanted colorectal cancer in nude mice.

机构信息

Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.

Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.

出版信息

PLoS One. 2019 Feb 21;14(2):e0201504. doi: 10.1371/journal.pone.0201504. eCollection 2019.

Abstract

This study aimed to explore the efficacy and mechanism of Chanling Gao (CLG), a compound Chinese medicine, on colorectal cancer (CRC). A model of transplanted CRC was established in nude mice. The mice were treated 7 days after CRC transplantation with either Capecitabine or CLG for 3 weeks. On the 28th day after the operation, CRC growth and liver metastasis were assessed by morphology, the changes in the expression of HIF-1α (hypoxia inducible factor-1α), stromal cell-derived factor-1 alpha (SDF-1α), CXCR4 (C-X-C chemokine receptor type 4), PI3K, and Akt in the transplanted tumor and SDF-1α and CXCR4 in the liver were detected by Western blot and immunohistochemistry. The protein contents of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and collagen IV in the serum and transplanted tumor and SDF-1α and CXCR4 in liver tissues were detected by enzyme-linked immunosorbent assay. In the Capecitabine and high dose CLG groups, the growth and liver metastasis of CRC were significantly inhibited, the protein levels of HIF-1α, SDF-1α, CXCR4, MMP-2, VEGF, PI3K, Akt, P-PI3K and P-Akt in the transplanted tumor were lower, while the content of collagen IV in the transplanted tumor was higher, than in Model group. A high dose of CLG inhibited the growth of transplanted tumor and liver metastasis of CRC in nude mice, probably by inhibiting the HIF-1α/SDF-1α-CXCR4/PI3K-Akt signaling pathway reducing the synthesis and release of VEGF and degradation of collagen IV.

摘要

本研究旨在探讨复方中药肠瘤宁(CLG)对结直肠癌(CRC)的疗效及作用机制。建立裸鼠 CRC 移植模型,CRC 移植后 7 天开始用卡培他滨或 CLG 治疗 3 周。术后第 28 天,通过形态学评估 CRC 生长和肝转移,Western blot 和免疫组化检测移植瘤中 HIF-1α(缺氧诱导因子-1α)、基质细胞衍生因子-1α(SDF-1α)、CXCR4(C-X-C 趋化因子受体 4)、PI3K 和 Akt 的表达变化,检测肝组织中 SDF-1α 和 CXCR4 的表达变化。通过酶联免疫吸附试验检测血清和移植瘤中血管内皮生长因子(VEGF)、基质金属蛋白酶-2(MMP-2)和胶原 IV 的蛋白含量,以及肝组织中 SDF-1α 和 CXCR4 的蛋白含量。卡培他滨和高剂量 CLG 组显著抑制 CRC 的生长和肝转移,移植瘤中 HIF-1α、SDF-1α、CXCR4、MMP-2、VEGF、PI3K、Akt、P-PI3K 和 P-Akt 的蛋白水平降低,而移植瘤中胶原 IV 的含量升高,与模型组相比。高剂量 CLG 抑制裸鼠移植瘤和 CRC 肝转移的生长,可能是通过抑制 HIF-1α/SDF-1α-CXCR4/PI3K-Akt 信号通路,减少 VEGF 的合成和释放以及胶原 IV 的降解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c1/6383928/839c2a8eb5b7/pone.0201504.g001.jpg

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