Image2_HDC downregulation induced by chronic stress promotes ovarian cancer progression via the IL-6/STAT3/S100A9 pathway.TIF
Objective<p>This study aimed to investigate the underlying mechanism of chronic stress promoting ovarian cancer growth comorbid with depression and evaluate the potential role of histamine (HIS) in treating this comorbidity.</p>Methods<p>Chronic unpredictable mild stress (CUMS) was...
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2024
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| _version_ | 1852024568315641856 |
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| author | Zhicong Chen (231442) |
| author2 | Jinming Cao (7837883) Zhijun Xiao (4926139) Zhen Yang (107412) Yuanchi Cheng (11221938) Jingjing Duan (1423531) Ting Zhou (38572) Feng Xu (89016) |
| author2_role | author author author author author author author |
| author_facet | Zhicong Chen (231442) Jinming Cao (7837883) Zhijun Xiao (4926139) Zhen Yang (107412) Yuanchi Cheng (11221938) Jingjing Duan (1423531) Ting Zhou (38572) Feng Xu (89016) |
| author_role | author |
| dc.creator.none.fl_str_mv | Zhicong Chen (231442) Jinming Cao (7837883) Zhijun Xiao (4926139) Zhen Yang (107412) Yuanchi Cheng (11221938) Jingjing Duan (1423531) Ting Zhou (38572) Feng Xu (89016) |
| dc.date.none.fl_str_mv | 2024-12-10T04:05:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fphar.2024.1485885.s002 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/figure/Image2_HDC_downregulation_induced_by_chronic_stress_promotes_ovarian_cancer_progression_via_the_IL-6_STAT3_S100A9_pathway_TIF/27998168 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Pharmacology Basic Pharmacology Clinical Pharmacology and Therapeutics Clinical Pharmacy and Pharmacy Practice Pharmaceutical Sciences Pharmacogenomics Toxicology (incl. Clinical Toxicology) Pharmacology and Pharmaceutical Sciences not elsewhere classified histidine decarboxylase histamine depression ovarian cancer chronic stress |
| dc.title.none.fl_str_mv | Image2_HDC downregulation induced by chronic stress promotes ovarian cancer progression via the IL-6/STAT3/S100A9 pathway.TIF |
| dc.type.none.fl_str_mv | Image Figure info:eu-repo/semantics/publishedVersion image |
| description | Objective<p>This study aimed to investigate the underlying mechanism of chronic stress promoting ovarian cancer growth comorbid with depression and evaluate the potential role of histamine (HIS) in treating this comorbidity.</p>Methods<p>Chronic unpredictable mild stress (CUMS) was used to establish a comorbid mouse model of ovarian cancer and depression. The behavioral phenotypes were assessed using the sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open field test (OFT). Ovarian cancer growth was monitored by tracking the tumor volume and weight. Histidine decarboxylase (HDC) expression in the tumor tissue was analyzed using Western blot and qRT-PCR techniques. The serum levels of inflammatory factors (IL-6 and IL-17A), stress hormones (norepinephrine, NE and cortisol, and COR), histamine, and 5-hydroxytryptamine (5-HT) were detected by enzyme-linked immunosorbent assay (ELISA). In vitro experiments were conducted to explore the direct impacts of stress hormones on A2780 and ES-2 ovarian cancer cell lines, as well as the modulation of these effects by histamine. HDC knockdown and overexpression approaches were used to study its regulatory role in the IL-6/STAT3/S100A9 signaling pathway.</p>Results<p>Chronic stress not only induced depressive behaviors but also accelerated ovarian cancer growth in mice by downregulating HDC expression in tumors, whereas exogenous HIS treatment alleviated depressive symptoms, suppressed cancer growth, and countered the decreased levels of HIS and increased levels of IL-6, IL-17A, NE, COR, and 5-HT induced by CUMS. Furthermore, HIS positively modulated the immune response by increasing the populations of CD3<sup>+</sup>T and CD8<sup>+</sup> T cells and reducing IL-17A secretion. In vitro experiments revealed that stress hormones downregulated HDC expression, consequently promoting cancer cell proliferation, migration, and invasion via the IL-6/STAT3/S100A9 pathway. Knockdown of HDC activated this pathway, whereas HDC overexpression inhibited its activation.</p>Conclusion<p>Chronic stress leads to the downregulation of HDC expression, thereby facilitating the progression of ovarian cancer through the IL-6/STAT3/S100A9 pathway. HIS might serve as a potential molecule for treating the comorbidities of ovarian cancer and depression.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_7c7bb0ba9bf1c2dc02f054d4e2cb72b3 |
| identifier_str_mv | 10.3389/fphar.2024.1485885.s002 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/27998168 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Image2_HDC downregulation induced by chronic stress promotes ovarian cancer progression via the IL-6/STAT3/S100A9 pathway.TIFZhicong Chen (231442)Jinming Cao (7837883)Zhijun Xiao (4926139)Zhen Yang (107412)Yuanchi Cheng (11221938)Jingjing Duan (1423531)Ting Zhou (38572)Feng Xu (89016)PharmacologyBasic PharmacologyClinical Pharmacology and TherapeuticsClinical Pharmacy and Pharmacy PracticePharmaceutical SciencesPharmacogenomicsToxicology (incl. Clinical Toxicology)Pharmacology and Pharmaceutical Sciences not elsewhere classifiedhistidine decarboxylasehistaminedepressionovarian cancerchronic stressObjective<p>This study aimed to investigate the underlying mechanism of chronic stress promoting ovarian cancer growth comorbid with depression and evaluate the potential role of histamine (HIS) in treating this comorbidity.</p>Methods<p>Chronic unpredictable mild stress (CUMS) was used to establish a comorbid mouse model of ovarian cancer and depression. The behavioral phenotypes were assessed using the sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open field test (OFT). Ovarian cancer growth was monitored by tracking the tumor volume and weight. Histidine decarboxylase (HDC) expression in the tumor tissue was analyzed using Western blot and qRT-PCR techniques. The serum levels of inflammatory factors (IL-6 and IL-17A), stress hormones (norepinephrine, NE and cortisol, and COR), histamine, and 5-hydroxytryptamine (5-HT) were detected by enzyme-linked immunosorbent assay (ELISA). In vitro experiments were conducted to explore the direct impacts of stress hormones on A2780 and ES-2 ovarian cancer cell lines, as well as the modulation of these effects by histamine. HDC knockdown and overexpression approaches were used to study its regulatory role in the IL-6/STAT3/S100A9 signaling pathway.</p>Results<p>Chronic stress not only induced depressive behaviors but also accelerated ovarian cancer growth in mice by downregulating HDC expression in tumors, whereas exogenous HIS treatment alleviated depressive symptoms, suppressed cancer growth, and countered the decreased levels of HIS and increased levels of IL-6, IL-17A, NE, COR, and 5-HT induced by CUMS. Furthermore, HIS positively modulated the immune response by increasing the populations of CD3<sup>+</sup>T and CD8<sup>+</sup> T cells and reducing IL-17A secretion. In vitro experiments revealed that stress hormones downregulated HDC expression, consequently promoting cancer cell proliferation, migration, and invasion via the IL-6/STAT3/S100A9 pathway. Knockdown of HDC activated this pathway, whereas HDC overexpression inhibited its activation.</p>Conclusion<p>Chronic stress leads to the downregulation of HDC expression, thereby facilitating the progression of ovarian cancer through the IL-6/STAT3/S100A9 pathway. HIS might serve as a potential molecule for treating the comorbidities of ovarian cancer and depression.</p>2024-12-10T04:05:00ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.3389/fphar.2024.1485885.s002https://figshare.com/articles/figure/Image2_HDC_downregulation_induced_by_chronic_stress_promotes_ovarian_cancer_progression_via_the_IL-6_STAT3_S100A9_pathway_TIF/27998168CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/279981682024-12-10T04:05:00Z |
| spellingShingle | Image2_HDC downregulation induced by chronic stress promotes ovarian cancer progression via the IL-6/STAT3/S100A9 pathway.TIF Zhicong Chen (231442) Pharmacology Basic Pharmacology Clinical Pharmacology and Therapeutics Clinical Pharmacy and Pharmacy Practice Pharmaceutical Sciences Pharmacogenomics Toxicology (incl. Clinical Toxicology) Pharmacology and Pharmaceutical Sciences not elsewhere classified histidine decarboxylase histamine depression ovarian cancer chronic stress |
| status_str | publishedVersion |
| title | Image2_HDC downregulation induced by chronic stress promotes ovarian cancer progression via the IL-6/STAT3/S100A9 pathway.TIF |
| title_full | Image2_HDC downregulation induced by chronic stress promotes ovarian cancer progression via the IL-6/STAT3/S100A9 pathway.TIF |
| title_fullStr | Image2_HDC downregulation induced by chronic stress promotes ovarian cancer progression via the IL-6/STAT3/S100A9 pathway.TIF |
| title_full_unstemmed | Image2_HDC downregulation induced by chronic stress promotes ovarian cancer progression via the IL-6/STAT3/S100A9 pathway.TIF |
| title_short | Image2_HDC downregulation induced by chronic stress promotes ovarian cancer progression via the IL-6/STAT3/S100A9 pathway.TIF |
| title_sort | Image2_HDC downregulation induced by chronic stress promotes ovarian cancer progression via the IL-6/STAT3/S100A9 pathway.TIF |
| topic | Pharmacology Basic Pharmacology Clinical Pharmacology and Therapeutics Clinical Pharmacy and Pharmacy Practice Pharmaceutical Sciences Pharmacogenomics Toxicology (incl. Clinical Toxicology) Pharmacology and Pharmaceutical Sciences not elsewhere classified histidine decarboxylase histamine depression ovarian cancer chronic stress |