Tags

Type your tag names separated by a space and hit enter

STAT3 inhibitory stattic enhances immunogenic cell death induced by chemotherapy in cancer cells.
Daru 2020DARU

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.

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 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.

CONCLUSION

These findings indicate that STAT3 inhibitory stattic can increase ICD induced by DOX. Graphical abstract.

Authors+Show Affiliations

Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.Faculty of Pharmacy and Pharmaceutical Science, University of Alberta, Edmonton, Canada.Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. omolavi@ualberta.ca. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. omolavi@ualberta.ca. Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran. omolavi@ualberta.ca.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31942696

Citation

Jafari, Sevda, et al. "STAT3 Inhibitory Stattic Enhances Immunogenic Cell Death Induced By Chemotherapy in Cancer Cells." Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2020.
Jafari S, Lavasanifar A, Hejazi MS, et al. STAT3 inhibitory stattic enhances immunogenic cell death induced by chemotherapy in cancer cells. Daru. 2020.
Jafari, S., Lavasanifar, A., Hejazi, M. S., Maleki-Dizaji, N., Mesgari, M., & Molavi, O. (2020). STAT3 inhibitory stattic enhances immunogenic cell death induced by chemotherapy in cancer cells. Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences, doi:10.1007/s40199-020-00326-z.
Jafari S, et al. STAT3 Inhibitory Stattic Enhances Immunogenic Cell Death Induced By Chemotherapy in Cancer Cells. Daru. 2020 Jan 16; PubMed PMID: 31942696.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - STAT3 inhibitory stattic enhances immunogenic cell death induced by chemotherapy in cancer cells. AU - Jafari,Sevda, AU - Lavasanifar,Afsaneh, AU - Hejazi,Mohammad Saied, AU - Maleki-Dizaji,Nasrin, AU - Mesgari,Mehran, AU - Molavi,Ommoleila, Y1 - 2020/01/16/ PY - 2019/08/02/received PY - 2020/01/07/accepted PY - 2020/1/17/entrez KW - Chemotherapy KW - Colon cancer KW - Combination therapy KW - Immunotherapy KW - Melanoma KW - STAT3 JF - Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences JO - Daru N2 - 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 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. CONCLUSION: These findings indicate that STAT3 inhibitory stattic can increase ICD induced by DOX. Graphical abstract. SN - 2008-2231 UR - https://www.unboundmedicine.com/medline/citation/31942696/STAT3_inhibitory_stattic_enhances_immunogenic_cell_death_induced_by_chemotherapy_in_cancer_cells L2 - https://darujps.biomedcentral.com/articles/10.1007/s40199-020-00326-z DB - PRIME DP - Unbound Medicine ER -