Combination of Astragali Polysaccharide and Curcumin Improves the Morphological Structure of Tumor Vessels and Induces Tumor Vascular Normalization to Inhibit the Growth of Hepatocellular Carcinoma

Abstract

Normalizing the disordered tumor vasculature, rather than blocking it, is a novel method for anticancer therapy. Astragali polysaccharide (APS) and curcumin were reported to be active against carcinomas. However, the effect and mechanism of the combination of APS and curcumin on vascular normalization in hepatocellular carcinoma (HCC) was not clear. In the present study, effects of combined APS and curcumin on tumor vascular normalization were evaluated in HepG2 tumor-bearing mice. Photoacoustic tomography (PAT) was performed to observe the morphological structure of tumor vessels in vivo. The microstructure of the tumor vessels was also analyzed through scanning electron microscopy. Additionally, the expression of CD31 and NG2 was analyzed by immunohistochemical staining. Tumor vessels of HepG2 tumor-bearing mice treated with the combination were sparse with uniform growth, morphology rules, and complete vascular walls, which had fewer branches and sprouts. ECs of tumor vessels were arranged regularly and were tightly connected, tending toward normalization. The expression of CD31 was reduced while NG2 was increased significantly by the combination of APS and curcumin. The results indicated that APS and curcumin in combination showed a better effect on inhibiting tumor growth in an orthotopic nude-mouse model of HCC. More important, the combination induced normalization of tumor vascular better than APS or curcumin administration alone, improving the morphological structure of tumor vessels and promoting maturation of tumor vessels. The results of the present study provided a reasonable possibility for combination therapy of APS and curcumin in the treatment of HCC via tumor vascular normalization.

Curcumin inhibits the growth of liver cancer by impairing myeloid‑derived suppressor cells in murine tumor tissues

“…Similarly, numerous previous in vitro and in vivo studies have demonstrated that curcumin inhibits the growth cancer in both animals and humans ( 40 – 42 ), including hepatocellular carcinoma ( 43 ). Several reports have suggested that curcumin or its derivative alone or in combination with other drugs exhibit favorable anti-liver cancer activity ( 44 – 46 ). Shao et al ( 47 ) reported that bisdemethoxycurcumin, a natural dimethoxy derivative of curcumin, decreases the number of tumor-infiltrating MDSCs in MB49 metastasized bladder cancer cells.…”

Standardized Astragalus Mongholicus Bunge-Curcuma Aromatica Salisb. Extract Efficiently Suppresses Colon Cancer Progression Through Gut Microbiota Modification in CT26-Bearing Mice

“…[Zingiberaceae; Curcumae Rhizoma] (ACE) produced synergistic effects on promoting the extract of bioactive ingredients, such as curcumenol, curdione, isocurcumenol, furanodienone, curcumol, and germacrone ( Yin et al, 2018 ). And the ACE intervention showed a good effect on lung, liver, and colon cancers and was particularly effective in inhibiting liver metastases from colon cancer ( Tang et al, 2019 ; Sun et al, 2021 ). However, whether the inhibitory effect is related to gut microbiota regulation is still not clear.…”

Experimental study of the vascular normalization window for tumors treated with apatinib and the efficacy of sequential chemotherapy with apatinib in lung cancer‐bearing mice and patients

“…The traditional view was that antiangiogenic drugs can reduce the formation of tumor blood vessels, cause tumor necrosis, and "starve" tumors . However, in recent years, many preclinical and clinical studies have shown that the short‐term application of antiangiogenic drugs can have therapeutic effects, whereas long‐term use can lead to vascular necrosis in the central area of the tumor, which results in hypoxia and an acidic microenvironment and decreases the sensitivity of solid tumor cells to chemotherapy . In response to these clinical problems, Jain proposed the tumor vascular normalization theory, which suggests that tumor angiogenesis is a complex process in which the imbalance between proangiogenic factors and angiogenesis inhibitors is a key factor .…”