| Background Induction of immunogenic cell death (ICD) is considered a promising strategy for cancer immunotherapy. Stattic is
an inhibitor of STAT3, which is found constitutively active in many cancers and plays a major role in cancer progression.
Objectives In the present study, we proposed to evaluate whether stattic can enhance the effects of chemotherapy in the induction
of ICD in cancer cells harboring hyperactive STAT3.
Methods The growth inhibitory effects of stattic and chemo agents including doxorubicin (DOX) and oxaliplatin (OXP) were
evaluated using MTT assay in B16F10 and CT26 cell lines. Flow cytometry was applied to study cell apoptosis and calreticulin
(CRT) surface exposure. The levels of high mobility group box 1 (HGMB1), heat shock protein70 (HSP70) and interleukin-12
(IL-12) were measured using ELISA.
Results Treatment of B16F10 and CT26 cells with stattic in combination with DOX resulted in synergistic antitumor effects with
combination index being 0.82 and 0.87, respectively. Interestingly, we found a higher level of ICD markers including CRT
expression as well as HMGB1 and HSP70 secretion in the cells received combination therapy of stattic and DOX as compared
with monotherapies.Moreover, exposure of dendritic cells (DCs) to conditionedmedia (CM) from cancer cells treated with stattic
and/or DOX resulted in secretion of IL-12, which is an indicator of DCs maturation and induction of Th1 response. OXP and
statticmonotherapy induced ICD in CT26 cells and stimulated IL-12 secretion by DCs; however, we did not observe a significant
increase in the level of ICD in CT26 cells and IL-12 secretion by DCs when CT26 cells were treated with stattic and OXP
combination as compared with monotherapy groups.
Conclusion These findings indicate that STAT3 inhibitory stattic can increase ICD induced by DOX. |