A novel strategy to enhance inhibition of Hela cervical cancer by combining Lentinus β-glucan and autophagic flux blockage.

Lentinus β-D-glucan (LNT), derived from artificially cultured mushrooms of Lentinus edodes, shows an important yet incompletely understood biological functions in cancer. In this work, the chemical structure of the refined LNT comprising a β-D-(1, 6)-branched β-D-(1,3)-glucan was further clarified via 1D- and 2D-NMR with high resolution, and its drug resistance resulted from autophagy in human cervical cancer (CC) Hela cells besides its anti-cancer function were revealed in vitro and in vivo. In detail, LNT destroyed cellular homeostasis by significantly increasing the intracellular Ca levels and promoted autophagic flux in vitro Hela cells, which was found to at least partially depend on the PI3K/Akt/mTOR-mediated pathway by up-regulating LC3-II levels and down-regulating the expression of p62, PI3K, p-Akt, and mTOR in Hela cells-transplanted BALB/c nude mice. In particular, LNT-induced autophagy led to a drug resistance against LNT-induced proliferation inhibition and apoptosis in Hela cells, and the co-treatment of autophagy inhibitors and LNT significantly enhanced the inhibition of Hela cells and tumor growth in vitro and in vivo. Therefore, the combination of LNT and autophagy inhibitors will be a novel therapeutic strategy to reduce the resistance and improve the prognosis of CC patients in the clinical.