Treatment for tumors depends on host immune system. The antitumor and immunoregulatory activities of Ulva lactuca polysaccharide (ULP) were evaluated in H22 tumorbearing mice and cyclophosphamide-induced immunosuppressed mice, respectively.The structural properties of ULP were identified through multi-angle laser light scattering, high-performance liquid chromatography, Fourier-transformed infrared, and nuclear magnetic resonance. It was composed of -D-Manp-(1→, →2,4)--L-Rhap-(1→, -D-GlcpA-(1→, -GalpA-(1→, →2,4)--D-Glcp-(1→, and →6)--D-Galp-(1→ with the molecular weight of 1.46 × 10 5 Da. Its antioxidant, anti-inflammatory, and antitumor effects were determined. Liver and tumor tissues were collected for histopathological, immunohistochemical, and western blotting analysis. ULP showed the great tumor growth inhibition of 74.41% compared with cyclophosphamide, which has side effects This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. c ○ 2020 The Authors. Food Frontiers published Food Frontiers. 2020;1:83-101. wileyonlinelibrary.com/journal/fft2 83 84 ZHAO ET AL. on immune system. ULP enhanced the expression of p53 to inhibit tumorigenesis, promoted the activation of IKK , and inhibited the activation of p65 within the NF-B pathway. ULP inhibited the tumor growth through downregulating the expressions of PI3K/Akt and mTOR, and promoting BAX/Bcl-2 ratio. The inhibition of TRAF2/TNF-and CD31/VEGF achieved a direct killing effect on tumor cells and inhibited tumor proliferation by inhibiting angiogenesis, respectively. Moreover, ULP increased the levels of immunoglobulin M and total superoxide dismutase, decreased the level of methane dicarboxylic aldehyde, and inhibited the activation of PI3K/AKT/mTOR/p70S6k pathways. The results showed that ULP exhibited pronounced antitumor activity and immunoregulatory effect. K E Y W O R D Santitumor, green alga, immunoregulation, structure, Ulva lactuca, ulvan
