Abstract
Abstract Cryptotanshinone (CT), isolated, purified and crystalized from the dried roots of Salvia militorrhiza, has been reported to have cytotoxic antitumor effects on a human liver cancer cell line in vitro. However, we have shown that CT also has immunoadjuvant effects and augments Th1 antitumor immunity. CT inhibited the proliferation of mouse hepatoma (Hepa1-6) cells by inducing Hepa1-6 cells apoptosis by dose dependent inhibition of the STAT3 signaling pathway. Furthermore, CT could also induce RAW264.7 cells polarize toward a M1 phenotype presumably with cytotoxic anti-tumor effects. CT was effective in the treatment of established Hepa1-6 hepatoma tumors in mice in combination with anti-PD-L1, and can cure Hepa1-6-bearing mice with the induction of subsequent anti-Hepa1-6 specific long-term immunity. Our data indicate that CT and anti-PD-L1 result in an effective immunotherapeutic regimen for the treatment of human hepatocellular carcinoma (HCC) based both on the cytotoxic effects and induction of immunity to the tumor.
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