Mechanism of bioactive polysaccharide from Lachnum sp. acts synergistically with 5‐fluorouracil against human hepatocellular carcinoma.

The antimetabolite 5‐fluorouracil (5‐FU) is a widely used antitumor agent, however the overall response rate to 5‐FU as a single agent is usually limited. Herein, how Lachnum expolysaccharide (LEP‐2a), a type of active polysaccharide isolated from Lachnum sp., acted synergistically with 5‐FU on HepG2 cells was investigated. It was found that LEP‐2a notably enhanced 5‐FU sensitivity in HepG2 cells in a synergistic manner. After combination treatment of 5‐FU and LEP‐2a, Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathway were inactivated. In addition, combination treatment induced generation of reactive oxygen species, decreased the levels of intracellular antioxidant enzymes and triggered mitochondrial apoptosis pathway. Furthermore, 5‐FU combined with LEP‐2a also resulted in p53 activation and NF‐κB inhibition, and cell cycle arrest in the S phase as well as cell metastasis stagnation. Interestingly, LEP‐2a treatment also blocked the DNA damage repair procedure. These findings demonstrate that LEP‐2a enhanced 5‐FU sensitivity and combination of 5‐FU and LEP‐2a exerts synergistic antitumor efficiency through multiple approaches. HIGHLIGHTS: 1.Lachnum expolysaccharide (LEP‐2a) possesses antitumor effect on HepG2 cells in vitro.2.LEP‐2a combined with 5‐fluorouracil (5‐FU) has a synergistic effect against HepG2 cells in vitro.3.The synergistic effect is mediated by the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathway.4.Reactive oxygen species (ROS) accumulation and the mitochondrial apoptosis pathway promote the effect.5.LEP‐2a blocks DNA damage repair and induces cell cycle arrest. [ABSTRACT FROM AUTHOR]