Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
PLoS One. 2019 Feb 21;14(2):e0201504. doi: 10.1371/journal.pone.0201504. eCollection 2019.
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.
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。