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.