Role of Integrin αvβ3 in Doxycycline-Induced Anti-Proliferation in Breast Cancer Cells

Chen, Yi-Fong; Yang, Yuanting; Chu, Hung-Ru; Huang, Tung-Yung; Wang, Shwu‐Huey; Chen, Hanyu; Li, Zi-Lin; Yang, Yuxing; Lin, Hung-Yun; Hercbergs, Aleck; Whang‐Peng, Jacqueline; Wang, Kuan; Davis, Paul J.

doi:10.3389/fcell.2022.829788

Cited by 10 publications

(8 citation statements)

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“…There is also clinical evidence that hypothyroidism is beneficial to the recovery of BC. Hercbergs et al proved that L-thyroxine, T4, was an in vitro proliferation factor of BC cells, and in the absence of estrogen, thyroid hormone could greatly help promote the proliferation of nuclear estrogen receptor- α - (ER α -) dependent BC cells [ 28 ]. At present, people have observed changes in serum protein glycosylation in several cancers including BC [ 29 ], which indicates that serum glycans may be potential biomarkers of BC.…”

Section: Discussionmentioning

confidence: 99%

HSPA5 Could Be a Prognostic Biomarker Correlated with Immune Infiltration in Breast Cancer

et al. 2022

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Background. Breast cancer (BC) is a frequent disease in females. The heat shock 70 kDa protein 5 (HSPA5) has recently been discovered to have an important function in tumor growth. However, the biological significance of HSPA5 in BC is unknown. Material and Method. Firstly, The Cancer Genome Atlas (TCGA) database was applied to analyze the expressions of HSPA5 in different cancer types, especially in BC. Then, the LinkedOmics database was used to screen genes coexpressed with HSPA5 in BC, presented by protein-protein interaction (PPI) and analyzed by functional enrichment analyses. Next, the Kaplan-Meier plotter was adopted to study the prognostic significance of HSPA5 and the relation between HSPA5 expression and different clinical factors in BC. Finally, the Tumor Immune Estimation Resource (TIMER) method was adopted to explore the relation between immune infiltration and HSPA5 in BC. Result. HSPA5 was highly expressed in most cancers, including BC. Genes coexpressed with HSPA5 were mainly related to endoplasmic reticulum unfolded protein response, melanosome, thyroid hormone synthesis, N-glycan biosynthesis, and so on. In the survival analysis, high HSPA5 expression indicated a poor prognosis in BC, and the expression of HSPA5 in BC was elevated after the incidence of BC, changing with different clinical factors. In the immune infiltration, HSPA5 was positively correlated with most immune cells. Conclusion. HSPA5 is an oncogene in BC progression, and it is connected with the prognosis and the immune infiltration in BC. Our findings suggest that HSPA5 could be an immunotherapy target and a prognostic biomarker in BC.

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Section: Discussionmentioning

confidence: 99%

HSPA5 Could Be a Prognostic Biomarker Correlated with Immune Infiltration in Breast Cancer

et al. 2022

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“…Doxycycline has been previously reported to have anti-tumor activity in multiple tumor models [5,7,32] including breast cancer [4,6,8,25,33]. It has also been shown to suppress expression of MMP2 and MMP9 [8,10,11,32], thus suggesting that measurement of these two MMP proteins could be a biological readout of doxycycline activity.…”

Section: Discussionmentioning

confidence: 99%

Doxycycline-Induced Changes in Circulating MMP or TIMP2 Levels Are Not Associated with Skeletal-Related Event-Free or Overall Survival in Patients with Bone Metastases from Breast Cancer

Zhao

Pond

Simos

et al. 2023

Cancers

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Doxycycline is often used as a promoter of inducible gene expression in preclinical models; however, it can also have direct effects on tumor growth and survival. This is due in part to its ability to inhibit cell invasion and regulate matrix metalloproteinase (MMP) expression. Given that doxycycline is also osteotropic, a clinical study to assess its effects on modulation of tumor progression or prevention of skeletal-related events (SRE) in patients with bone metastases from breast cancer (the Achilles trial) was undertaken. Patients received 100 mg of oral doxycycline twice daily for 12 weeks, with serum obtained at baseline and 4, 8 and 12 weeks post-initiation of doxycycline treatment. Exploratory analysis of the effects of doxycycline on circulating levels of MMP or tissue inhibitor of matrix metalloproteinase 2 (TIMP2) was performed in enrolled patients. Statistically significant associations were observed between MMP2, MMP9 and TIMP2 at baseline with significant associations maintained between absolute levels and changes in levels of MMP2 and TIMP2 at weeks 4–12 post initiation of doxycycline. Treatment with doxycycline generally resulted in decreases in MMP2 and MMP9 levels with concurrent upregulation of TIMP2 at 12 weeks post-initiation of doxycycline treatment. Despite this, we observed no association with the levels of any of these factors with either SRE-free or overall survival in this patient cohort. In summary, despite observing hypothesized effects of doxycycline administration on surrogate markers of its anti-tumor activity, measures of circulating levels of these biomarkers were not prognostic in this patient population.

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“…Western blot analyses were conducted as previously described ( Chen et al, 2022 ). The ovaries from 28 to 36 weeks aged-old female mice were harvested in the young mice groups.…”

Section: Methodsmentioning

confidence: 99%

2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-Glucoside improves female ovarian aging

Lin

Yang

Chen

et al. 2022

Front. Cell Dev. Biol.

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Reduced fertility associated with normal aging may reflect the over-maturity of oocytes. It is increasingly important to reduce aging-induced infertility since recent trends show people marrying at later ages. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG), a polyphenol extracted from Polygonum multiflorum, has been reported to have anti-inflammatory and anti-aging properties. To evaluate whether THSG can reduce aging-related ovarian damage in a female mouse model of aging, THSG was administered by gavage at a dose of 10 mg/kg twice weekly, starting at 4 weeks of age in a group of young mice. In addition, the effect of THSG in a group of aged mice was also studied in mice starting at 24 weeks of age. The number of oocytes in the THSG-fed group was higher than in the untreated control group. Although the percentage of secondary polar bodies (PB2) decreased during aging in the THSG-fed group, it decreased much more slowly than in the age-matched control group. THSG administration increased the quality of ovaries in young mice becoming aged. Western blotting analyses also indicated that CYP19, PR-B, and ER-β expressions were significantly increased in 36-week-old mice. THSG also increased oocyte numbers in aged mice compared to mice without THSG fed. Studies of qPCR and immunohistochemistry (IHC) analyses of ovaries in the aged mice groups were conducted. THSG increased gene expression of anti-Müllerian hormone (AMH), a biomarker of oocyte number, and protein accumulation in 40-week-old mice. THSG increased the expression of pgc1α and atp6, mitochondrial biogenesis-related genes, and their protein expression. THSG also attenuated the fading rate of CYP11a and CYP19 associated with sex hormone synthesis. And THSG maintains a high level of ER-β expression, thereby enhancing the sensitivity of estrogen. Our findings indicated that THSG increased or extended gene expression involved in ovarian maintenance and rejuvenation in young and aged mice. On the other hand, THSG treatments significantly maintained oocyte quantity and quality in both groups of young and aged mice compared to each age-matched control group. In conclusion, THSG can delay aging-related menopause, and the antioxidant properties of THSG may make it suitable for preventing aging-induced infertility.

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Role of Integrin αvβ3 in Doxycycline-Induced Anti-Proliferation in Breast Cancer Cells

Cited by 10 publications

References 50 publications

HSPA5 Could Be a Prognostic Biomarker Correlated with Immune Infiltration in Breast Cancer

HSPA5 Could Be a Prognostic Biomarker Correlated with Immune Infiltration in Breast Cancer

Doxycycline-Induced Changes in Circulating MMP or TIMP2 Levels Are Not Associated with Skeletal-Related Event-Free or Overall Survival in Patients with Bone Metastases from Breast Cancer

2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-Glucoside improves female ovarian aging

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