Pien Tze Huang inhibits tumor angiogenesis in a mouse model of colorectal cancer via suppression of multiple cellular pathways
Pien Tze Huang inhibits tumor angiogenesis in a mouse model of colorectal cancer via suppression of multiple cellular pathways
复制标题
片仔癀通过抑制多种细胞途径抑制结直肠癌小鼠模型中的肿瘤血管生成
DOI：
10.3892/or.2013.2609
复制
发表时间：
2013-10-01
期刊：
影响因子：
4.2
通讯作者：
Peng, Jun
中科院分区：
文献类型：
--
作者：
Shen, Aling;Lin, Jiumao;Peng, Jun
血管生成在癌症进展中起着重要作用，因此已成为抗癌治疗的一个有吸引力的靶点。肿瘤血管生成受到多种信号通路的严格调控，这些信号通路通常是冗余的；此外，这些通路之间的串扰形成了一个由代偿机制调节的复杂网络。鉴于肿瘤血管生成致病机制的复杂性，目前大多数仅针对单一途径的血管生成抑制剂可能不足，并可能产生耐药性，因此增加了开发新型抗癌药物的必要性。由于副作用相对较少，并且数千年来一直用于临床治疗包括癌症在内的各种疾病，传统中药（TCM）正受到极大的关注。片仔黄（PZH）是一种著名的传统中药，450年前首次被开处方，长期以来一直被用作治疗癌症的替代药物。然而，PZH抗肿瘤活性的确切机制仍有待进一步阐明。在本研究中，我们利用结直肠癌小鼠异种移植模型，评估了PZH对肿瘤血管生成的影响，并探讨了其潜在的分子机制。我们发现PZH抑制肿瘤生长，因为PZH治疗导致结直肠癌小鼠肿瘤体积和肿瘤重量下降。此外，PZH抑制STAT3、Akt和MAPKs等多种信号通路的激活。因此，PZH对这些通路的抑制作用导致肿瘤血管生成的抑制，表现为肿瘤组织微血管密度的降低。此外，PZH治疗降低了血管生成因子包括iNOS、eNOS、VEGF-A、bFGF及其特异性受体VEGFR2和bFGFR的表达。总之，我们的研究结果表明，通过抑制多种信号通路抑制肿瘤血管生成可能是PZH影响癌症的机制之一。
Angiogenesis plays an essential role in cancer progression, which therefore has become an attractive target for anticancer treatment. Tumor angiogenesis is tightly regulated by multiple signaling pathways that usually function redundantly; in addition, crosstalk between these pathways forms a complicated network that is regulated by compensatory mechanisms. Given the complexity of pathogenic mechanisms underlying tumor angiogenesis, most currently used angiogenesis inhibitors that only target single pathways may be insufficient and probably generate drug resistance, thus, increasing the necessity for development of novel anticancer agents. Traditional Chinese medicines (TCM) are receiving great interest since they have relatively fewer side-effects and have been used for thousands of years to clinically treat various types of diseases including cancer. Pien Tze Huang (PZH), a well-known traditional Chinese formulation that was first prescribed 450 years ago, has long been used as an alternative remedy for cancers. However, the precise mechanism of PZH's anticancer activity remains to be further elucidated. Using a colorectal cancer mouse xenograft model, in the present study, we evaluated the effect of PZH on tumor angiogenesis and investigated the underlying molecular mechanisms. We found that PZH inhibited tumor growth since PZH treatment resulted in decrease in both tumor volume and tumor weight in CRC mice. In addition, PZH suppressed the activation of several signaling pathways such as STAT3, Akt and MAPKs. Consequently, the inhibitory effect of PZH on these pathways resulted in the inhibition of tumor angiogenesis as demonstrated by the decrease of microvessel density in tumor tissues. Moreover, PZH treatment reduced the expression of angiogenic factors including iNOS, eNOS, VEGF-A, bFGF as well as their specific receptors VEGFR2 and bFGFR. Altogether, our findings suggest that inhibition of tumor angiogenesis via suppression of multiple signaling pathways might be one of the mechanisms whereby PZH affects cancers.