ABSTRACT
Macrophages are the most abundant cells in tumor stroma and their polarization within tumor microenvironment exert the key roles in tumorigenesis. Astragaloside IV is a natural extract from traditional Chinese herbal Radix Astragali, and fulfills pleiotropic function in several cancers. Nevertheless, its function in ovarian cancer microenvironment remains elusive. In the present research, astragaloside IV exhibited little cytotoxicity within a certain dose range in THP-1 cells. Moreover, astragaloside IV suppressed the ratio of CD14+CD206+ cells in IL-4/IL-13-treated THP-1 macrophages and transcripts of M2 macrophage markers (including CD206, CCL24, PPARγ, Arg-1, IL-10), indicating the inhibitory effects of astragaloside IV on IL-4/IL-13-induced macrophage M2 polarization. Intriguingly, astragaloside IV antagonized M2 macrophages coculture-evoked cell proliferation, invasion and migration in ovarian cancer cells. During this process, administration with astragaloside IV restrained the high expression of high-mobility group box1 (HMGB1) and TLR4 in macrophages co-cultured with ovarian cancer cells, concomitant with decreases in release of M2 marker TGF-ß, MMP-9 and IL-10. Moreover, targeting the HMGB1 signaling reversed M2 macrophages-induced ovarian cancer cell proliferation, invasion and migration. Noticeably, exogenous HMGB1 overturned the inhibitory efficacy of astragaloside IV against macrophage M2 polarization-evoked malignant potential in ovarian cancer cells. Together, these findings suggest that astragaloside IV may protect against M2 macrophages-evoked malignancy in ovarian cancer cells by suppressing the HMGB1-TLR4 signaling. Therefore, astragaloside may alleviate the progression of ovarian cancer by regulating macrophage M2 polarization within tumor microenvironment, implying a promising therapeutic strategy against ovarian cancer.
Subject(s)
Cell Polarity/drug effects , Macrophage Activation/drug effects , Macrophages/drug effects , Ovarian Neoplasms/pathology , Saponins/pharmacology , Triterpenes/pharmacology , Cell Movement/drug effects , Cell Polarity/immunology , Disease Progression , Female , HMGB1 Protein/metabolism , Humans , Macrophages/physiology , Ovarian Neoplasms/immunology , Ovarian Neoplasms/metabolism , Phenotype , Signal Transduction/drug effects , THP-1 Cells , Toll-Like Receptor 4/metabolism , Tumor Cells, Cultured , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunologyABSTRACT
Increasing evidence demonstrate that dysregulated microRNAs (miRNAs) are involved in carcinogenesis and tumor progression in papillary thyroid cancer (PTC). However, the specific miR-761 in cancer remains largely unknown. In this study, we reported for the first that miR-761 expression was down-regulated in PTC tissues and cell lines, and its decrease was associated with tumor size and TNM stage. Gain- and loss-of function experiments revealed that miR-761 inhibited cell proliferation, colony formation and cell cycle progression in vitro and in vivo. Moreover, TRIM29 was identified as a direct downstream target of miR-761 in PTC cells and mediated the functional effects of miR-761 in PTC. Restoration of TRIM29 expression at least partially abolished the biological effects of miR-761 on PTC cells. Furthermore, overexpression of lncRNA HOXA11-AS was inversely correlated with miR-761 expression in PTC tissues. LncRNA HOXA11-AS could modulate the miR-761 expression and regulate cellular behaviors. Taken together, this research supports the first evidence that lncRNA HOXA11-AS-reguated miR-761 plays a functional role in inhibiting PTC progression by targeting TRIM29 and represent a promising therapeutic strategy for patients with PTC.
ABSTRACT
Aim of this research work is to observe and analyze the clinical effect of total thyroidectomy combined with radioactive iodine in thyroid cancer treatment. The 120 thyroid cancer patients treated in our hospital were enrolled as study subjects and assigned to study group (treated with total thyroidectomy and radioactive iodine) and reference group (treated with conventional total thyroidectomy). The overall treatment efficacy was compared between the two groups. Comparison of overall treatment efficacy of the two groups showed that the study group has superior results to the reference group (P<0.05). Comparison of incidence of recurrent laryngeal nerve injury in the two groups revealed no significant differences, P>0.05. However, in life quality assessment, the study group was significantly superior to the reference group in terms of physiological function, psychological function, social function, and overall life quality scores, P<0.05. Total thyroidectomy combined with radioactive iodine can well improve the overall treatment efficiency and enable patients to have higher quality of life at the same time.
