Tags

Type your tag names separated by a space and hit enter

All-trans retinoic acid induces anti-tumor effects via STAT3 signaling inhibition in oral squamous cell carcinoma and oral dysplasia.

Abstract

BACKGROUND

Oral squamous cell carcinoma (OSCC), which may arise from oral dysplasia, is one of the most prevalent cancers around the world. In recent years, all-trans retinoic acid (ATRA) has showed great potential in cancer treatment. However, the molecular mechanism for the anti-tumor effects of ATRA remains unclear.

MATERIALS AND METHODS

After treated with ATRA, inhibition of cell proliferation of OSCC and oral dysplasia cell lines, CAL27 and DOK, respectively, was analyzed by a Cell Counting Kit-8 (CCK8) assay. The cell cycle arrest, cell apoptosis induction and PD-L1 expression level was measured by flowcytometry. A small molecular inhibitor was utilized to block STAT3 pathway and the related proteins expression was measured by Western Blot.

RESULTS

The present study demonstrated that ATRA inhibited cell proliferation at 5-75 μM, arrested cell cycle at S and G2-phase, induced apoptosis effect in OSCC and oral dysplasia cell line, CAL27 and DOK, respectively. ATRA led to inhibition of p-STAT3, p-JAK2, increased the level of p-ERK, and significantly decreased the PD-L1 expression. Moreover, targeting STAT3 signaling increased (P<0.001) the level of cleaved caspase-3, and effectively (P<0.001) decreased the expression of cyclin A2 and PD-L1. The effect of ATRA on cell growth inhibition, apoptosis induction and PD-L1 expression decrease was significantly (P<0.05) enhanced after the STAT3 signaling blockade.

CONCLUSION

These findings suggested that ATRA induced anti-tumor effects and downregulated PD-L1 expression via STAT3 signaling inhibition in both OSCC and oral dysplasia. This article is protected by copyright. All rights reserved.

Authors+Show Affiliations

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China. Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China. Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31323146

Citation

Chen, Xiao-Jie, et al. "All-trans Retinoic Acid Induces Anti-tumor Effects Via STAT3 Signaling Inhibition in Oral Squamous Cell Carcinoma and Oral Dysplasia." Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 2019.
Chen XJ, He MJ, Zhou G. All-trans retinoic acid induces anti-tumor effects via STAT3 signaling inhibition in oral squamous cell carcinoma and oral dysplasia. J Oral Pathol Med. 2019.
Chen, X. J., He, M. J., & Zhou, G. (2019). All-trans retinoic acid induces anti-tumor effects via STAT3 signaling inhibition in oral squamous cell carcinoma and oral dysplasia. Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, doi:10.1111/jop.12931.
Chen XJ, He MJ, Zhou G. All-trans Retinoic Acid Induces Anti-tumor Effects Via STAT3 Signaling Inhibition in Oral Squamous Cell Carcinoma and Oral Dysplasia. J Oral Pathol Med. 2019 Jul 19; PubMed PMID: 31323146.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - All-trans retinoic acid induces anti-tumor effects via STAT3 signaling inhibition in oral squamous cell carcinoma and oral dysplasia. AU - Chen,Xiao-Jie, AU - He,Ming-Jing, AU - Zhou,Gang, Y1 - 2019/07/19/ PY - 2019/7/20/entrez PY - 2019/7/20/pubmed PY - 2019/7/20/medline KW - All-trans retinoic acid KW - OSCC treatment KW - PD-L1 KW - STAT3 KW - oral dysplasia KW - oral squamous cell carcinoma JF - Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology JO - J. Oral Pathol. Med. N2 - BACKGROUND: Oral squamous cell carcinoma (OSCC), which may arise from oral dysplasia, is one of the most prevalent cancers around the world. In recent years, all-trans retinoic acid (ATRA) has showed great potential in cancer treatment. However, the molecular mechanism for the anti-tumor effects of ATRA remains unclear. MATERIALS AND METHODS: After treated with ATRA, inhibition of cell proliferation of OSCC and oral dysplasia cell lines, CAL27 and DOK, respectively, was analyzed by a Cell Counting Kit-8 (CCK8) assay. The cell cycle arrest, cell apoptosis induction and PD-L1 expression level was measured by flowcytometry. A small molecular inhibitor was utilized to block STAT3 pathway and the related proteins expression was measured by Western Blot. RESULTS: The present study demonstrated that ATRA inhibited cell proliferation at 5-75 μM, arrested cell cycle at S and G2-phase, induced apoptosis effect in OSCC and oral dysplasia cell line, CAL27 and DOK, respectively. ATRA led to inhibition of p-STAT3, p-JAK2, increased the level of p-ERK, and significantly decreased the PD-L1 expression. Moreover, targeting STAT3 signaling increased (P<0.001) the level of cleaved caspase-3, and effectively (P<0.001) decreased the expression of cyclin A2 and PD-L1. The effect of ATRA on cell growth inhibition, apoptosis induction and PD-L1 expression decrease was significantly (P<0.05) enhanced after the STAT3 signaling blockade. CONCLUSION: These findings suggested that ATRA induced anti-tumor effects and downregulated PD-L1 expression via STAT3 signaling inhibition in both OSCC and oral dysplasia. This article is protected by copyright. All rights reserved. SN - 1600-0714 UR - https://www.unboundmedicine.com/medline/citation/31323146/All-trans_retinoic_acid_induces_anti-tumor_effects_via_STAT3_signaling_inhibition_in_oral_squamous_cell_carcinoma_and_oral_dysplasia L2 - https://doi.org/10.1111/jop.12931 DB - PRIME DP - Unbound Medicine ER -