The heat shock transcription factor (HSF) is an important transactivator of the heat shock genes. Recent studies have shown that HSF1 acts as a repressor of non-heat shock genes to protect against endotoxemia. In this study, we found that heat shock treatment and HSF1 over-expression augmented the induction of interleukin (IL)-10 mRNA. Computational analysis of the mouse IL-10 promoter region showed that three potential heat shock elements (HSEs) were located at mouse IL-10 gene promoter, among which only the -387/-360 probe formed a complex with HSF1. The lack of binding of the other two HSEs to HSF1 suggested the critical role of the flanking sequences in the binding specificity of HSE to HSF1. Moreover, we showed that HSF1 overexpression transactivated mouse IL-10 gene promoter and this transcriptional activation was inhibited by the mutation of HSE in the -387/-360 region of IL-10 gene promoter using luciferase reporter assay. These findings indicate that HSF1 is a transcriptional activator of anti-inflammatory mediator IL-10 gene in RAW264.7 macrophages.
Background: A number of effective prevention measures have been introduced in attempts to substantially reduce both the incidence and mortality due to many kinds of cancer. The search for new anti-cancer compounds in foods or in plant medicines is one realistic and promising approach to prevention. Chinese medicines provide a rich pool of novel and efficacious agents for cancer prevention and treatment. Previously it was demonstratrated that hyperin extracted from the Manchurian rhododendron leaf reduces the proliferation of many cancer cells. The present study was carried out to evaluate its effects on human endometrial cancer cell viability and apoptosis and to investigate its mechanisms of action in RL952 cells. Methods: Cell viability was measured using the MTT assay. Intracellular calcium ions were detected using laser-scanning confocal microscopy. The effects of hyperin on apoptosis related proteins in RL952 cells were examined using Western blot analysis. Results: The growth of RL952 cells was inhibited by treatment with hyperin. OD values of caspase-3 and caspase-9 were increased and expression of bcl-2 was increased and bax was decreased in protein levels in RL952 cells after 24 h of hyperin treatment, Moreover, intracellular calcium accumulation occurred in hyperin-treated cells. Conclusions: These results suggest that hyperin may play an important role in tumor growth suppression by inducing apoptosis in human endometrial cells via a Ca 2+ -related mitochondrion apoptotic pathway in RL952 cells.
Objective. To study the expression and correlation of insulin receptor (INSR), insulin receptor substrate-1 (IRS-1), and programmed cell death ligand-1 (PD-L1) in nonsmall cell lung cancer (NSCLC). Methods. 45 lung cancer tissues and 30 adjacent normal tissues of NSCLC patients diagnosed in the Second Affiliated Hospital of Shandong First Medical University from June 2019 to August 2020 were selected. The expressions of INSR, IRS-1, and PD-L1 proteins in tumor tissues and adjacent tissues of NSCLC were detected by immunohistochemical staining. Results. The expression of INSR and IRS-1 in NSCLC was significantly higher than that in adjacent normal lung tissue (
P
<
0.05
). INSR expression had statistical significance with the degree of pathological differentiation of nonsmall cell carcinoma (
P
=
0.031
), but had no significant association with age, gender, pathological type, TNM stage, and lymph node metastasis status (
P
>
0.05
). There was no significant correlation between IRS-1 positive expression and NSCLC patients’ age, gender, pathological typing, degree of differentiation, TNM stage, and lymph node metastasis (
P
>
0.05
). PD-L1 positive expression was correlated with lymph node metastasis of NSCLC (
P
=
0.028
), while there was no significant correlation with gender, age, pathological type, TNM stage, and pathological differentiation degree of NSCLC patients (
P
>
0.05
). Spearman correlation analysis showed that PD-L1 protein expression had a significant positive correlation with IRS-1 protein expression (
r
=
0.373
), but was not correlated with the expression of INSR protein. Conclusion. IRS-1 may be involved in the regulation of PD-L1 expression and mediate the occurrence of tumor immune escape, which is expected to become a new target for NSCLC immunotherapy and provide new clinical evidence for immunosuppressive therapy.
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