Background: Anlotinib is a highly potent multi-target tyrosine kinase inhibitor, with very good anti-tumor activity against a variety of solid tumors. However, its effect on colorectal cancer (CRC) is not yet clearly understood. The objective of this study was to investigate the anti-tumor effect and underlying mechanism of anlotinib in the pathogenesis of CRC. Materials and Methods: Effects of anlotinib on CT26 cells proliferation and microvessel formation in endothelial cells were determined by MTT assay and tube formation assay. Cell migration and invasion were analyzed by using the wound healing assay and transwell assay. Cell cycle and apoptosis were detected by flow cytometry. A CRC xenograft mouse model was used for conducting in-vivo studies to verify the effect of anlotinib. The expression of Ki-67 and CD31 in the tumor tissue was detected by immunohistochemistry and protein expression was measured by Western blot. Results: In-vitro studies revealed that anlotinib inhibited the proliferation, migration, and invasion of CT26 cells and the tube formation of HUVECs in a dose-dependent manner. Anlotinib also significantly induced cell apoptosis and G2/M arrest. It effectively inhibited tumor growth and prolonged survival time in the CRC xenograft mouse model. Immunohistochemical analysis of the tumor tissue revealed that anlotinib downregulated CD31 and Ki-67 which are the biomarkers of microvessel density and proliferation. Furthermore, anlotinib was able to inhibit the activation of VEGFR-2/AKT and FGFR, PDGFRβ and their downstream signaling ERK. Conclusion:The findings of the present study suggested that anlotinib suppressed cell proliferation and angiogenesis via inhibition of AKT/ERK signaling pathway in colorectal cancer and could be a novel therapeutic strategy for treatment of CRC.

Background: This study investigated the relationship between thyroid diseases and the risk of breast cancer (BC). Clarifying this issue can help medical staff perform of early prevention, diagnosis and treatment for breast cancer patients. Methods:The meta-analysis combined data from cohort studies and case-control to obtain a comprehensive result of the relationship between thyroid diseases and risk of BC. We comprehensively searched PubMed, EMbase, Web of Science, and the Cochrane Library. The search period was from the establishment of the databases to August 2020. Literature was collected and screened individually by two reviewers. There was English language restriction on the search and unpublished literature was excluded.The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the selected studies prior to data extraction. The data collected included country, author, year of publication, research type, and number of cases. In cases where the data and study heterogeneity permitted, meta-analyses were performed, and odd ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Data were analyzed using the STATA 15.1 software.Results: A total of 21 articles were included in this study. Hyperthyroidism, thyroid cancer, thyroglobulin antibody (TGAb) levels, and thyroid microsomal antibody (TPOAb) levels were all significantly associated with an increased risk of BC, while hypothyroidism was associated with a reduced risk of BC.Conclusions: This study demonstrated that hyperthyroidism, autoimmune thyroiditis (AITD), and thyroid cancer are significantly associated with an increased risk of BC, while hypothyroidism is associated with a reduced risk of BC.

Vascular complications are the primary reason for disability and mortality associated with diabetes mellitus (dM), and numerous micrornas (mirnas/mirs) are involved in the process, such as mir-122, mir-24 and mir-423. it has been reported that mir-328 regulates dM and cardiovascular disease; however, the role and mechanism of action underlying mir-328 in HuVecs is not completely understood. The present study aimed to investigate the role and mechanism of action underlying the effects of mir-328 on the functions of HuVecs. To simulate hyperglycemia combined with ischemia-induced tissue starvation, HuVecs were cultured in endothelial cell medium with 25 mmol/l d-glucose and 2% FBS for 24 h [high glucose (HG) + 2% FBS group]. HuVec mir-328 expression levels were detected by reverse transcription-quantitative Pcr. cell migration, cytotoxicity and tube-like structure formation were analyzed using wound healing, cell counting Kit-8 and tube formation assays, respectively. Following transfection with mir-328 inhibitor, mir-328 expression was downregulated in HuVecs. Protein expression levels were determined by western blotting. compared with the control group, the migration and tube-like structure formation of HuVecs were decreased, and cell cytotoxicity was increased in the HG + 2% FBS group. The protein expression levels of vascular endothelial growth factor were also decreased, and the expression levels of mirna-328 in the HG + 2% FBS group were increased compared with the control group. However, mirna-328 downregulation reversed the aforementioned effects. Further experiments indicated that the aKT signaling pathway was inhibited in the HG + 2% FBS group; however, mir-328 downregulation activated the aKT/mTor signaling pathway, which was blocked by the aKT signaling pathway inhibitor, perifosine. Gene prediction and western blotting demonstrated that mir-328 displayed a regulatory role via Pim-1 proto-oncogene, serine/threonine kinase (PiM1). in conclusion, mir-328 expression was upregulated and angiogenesis was inhibited when HuVecs were subjected to high glucose and low serum conditions. mir-328 downregulation enhanced angiogenesis by increasing PiM1 expression and activating the aKT/mTor signaling pathway in HuVecs under high glucose and low serum conditions.

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