Back to Search
Start Over
STAT3 inhibitory stattic enhances immunogenic cell death induced by chemotherapy in cancer cells.
- Source :
-
Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences [Daru] 2020 Jun; Vol. 28 (1), pp. 159-169. Date of Electronic Publication: 2020 Jan 16. - Publication Year :
- 2020
-
Abstract
- 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.<br />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.<br />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.<br />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 conditioned media (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 stattic monotherapy 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.<br />Conclusion: These findings indicate that STAT3 inhibitory stattic can increase ICD induced by DOX. Graphical abstract.
- Subjects :
- Animals
Apoptosis drug effects
Cell Line, Tumor
Dendritic Cells drug effects
HMGB1 Protein metabolism
HSP70 Heat-Shock Proteins metabolism
Interleukin-12 metabolism
Mice, Inbred C57BL
Neoplasms drug therapy
Neoplasms metabolism
Antineoplastic Agents pharmacology
Cyclic S-Oxides pharmacology
Doxorubicin pharmacology
Immunogenic Cell Death drug effects
Oxaliplatin pharmacology
STAT3 Transcription Factor antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 2008-2231
- Volume :
- 28
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31942696
- Full Text :
- https://doi.org/10.1007/s40199-020-00326-z