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Background: Radioresistance remains a challenge for cancer radiotherapy. The present study aims to investigate the role of TMPRSS4 in triple negative breast cancer (TNBC) cell radiosensitivity. Materials and Methods: After transfection of MDA-MD-468 triple negative breast cancer cells line by using the lentivirus vector, the effect of TMPRSS4 down-regulation on TNBC radiosensitivity was evaluated by using cloning assay and CCK-8 assay. The CCK-8 assay was also used for performing cell proliferation analysis. Western blot was carried out to detect the expression of certain proteins related to cell cycle pathways (cyclin D1), cell apoptosis pathways (Bax, Bcl2, and Caspase3), DNA damage and DNA damage repair (TRF2, Ku80 , ˠH2AX). The cell cycle and cell apoptosis were also investigated using flow cytometer analysis. Results: TMPRSS4 expression was down-regulated in MDA-MB-468 cells which enhanced MDA-MB-468 cells radiosensitivity. TMPRSS4 silencing also improved IR induced cell proliferation ability reduction and promoted cell arrested at G2/M phase mediated by 6 Gy IR associated with cyclin D1 expression inhibition. Moreover, TMPRSS4 inhibition enhanced TNBC apoptosis induced by 6 Gy IR following by over-expression of (Bax, Caspase3) and down-regulation of Bcl2 as the pro-apoptotic and anti-apoptotic proteins, respectively. Otherwise, TMPRSS4 down-regulation increases DNA damage induced by 6 Gy IR and delays DNA damage repair respectively illustrated by downregulation of TRF2 and permanent increase of Ku80 and ˠH2AX expression at 1 h and 10 h post-IR. Conclusion: Down-regulation of TMPRSS4 increases triple negative breast cancer cell radiosensitivity and the use of TMPRSS4 inhibitor can be encouraged for improving radiotherapy effectiveness in TNBC radioresistant patients.

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Background: Abnormal lipid profile is common in subjects with type 2 diabetes (T2D). Despite use of lipidlowering agents, many subjects with T2D do not achieve lipid targets. The present work aimed to assess lipid profile in a randomly selected group of adult diabetic subjects under treatment in order to determine how diabetes treatment affects blood lipid parameters levels. HbA1c level is used as a biomarker of glycaemia control achievement and treatment success in diabetic. Methods: This study was carried out as a pre-post test design study with a control group. A total of 117 diabetic subjects under treatment and 100 non-diabetics as control subjects are included in the study. TC, TG and HDL-C were measured by enzymatic methods and LDL-C was determined by Friedewald formula. Plasma glucose was measured by Glucose Oxidase method and glycated hemoglobin (HbA1c) with a radioimmunoassay. Results:The results showed that TC (p<0.001), LDLc (p<0.001) and TG (p=0.02) levels increased significantly in diabetics compared to controls. Atherogenic indices TC/HDL-C (p<0.01) and LDL-C/HDL-C (p<0.01), and blood calcium level (p<0.001) were significantly increased in diabetics than in controls. Subjects with HbA1c value >7.0% had significantly higher levels of TC (P<0.01), LDL-C (p<0.05), TC/HDL-C (p<0.01), LDL-C/HDL-C (p=0.02), TG/HDL-C (p=0.01) and calcemia (p<0.001) compared to subjects with HbA1c ≤7.0%. Conclusion: Significant difference of lipid parameters was observed in diabetics with HbA1c ≤7.0% and >7.0%. Abnormal lipid patterns and insulin resistance tend to be normalized with therapy of diabetes.

Background: TMPRSS4 is a novel Type II transmembrane serine protease found at the surface of the cells and is involved in the development and cancer progression. However, TMPRSS4 functions in breast cancer remain poor understand. The present study investigated the function of TMPRSS4 in the breast cancer cells and the potential mechanistic action underling. Materials and Methods: The lentiviral vectors causing TMPRSS4 down-regulation and over-expression were established and transfected in MDA-MB-468 and MCF-7 cells, respectively. By using the CCK-8 assay, cell proliferation was analyzed. Moreover, western blot was used to detect the expression of certain proteins related to cell apoptosis (Bax and Bcl2) signaling pathway and telomere maintenance (POT1, TPP1, and UBE2D3). Cell cycle and cell apoptosis were also analyzed by using the Flow cytometry analysis. TMPRSS4 expression was detected at the mRNA level and protein level by performing qPCR and western blot technique, respectively. Results: TMPRSS4 expression is inhibited in stable transfected MDA-MB-468-shTMPRSS4 cells compared to the control MDA-MB-468-NC and its expression is up-regulated in stable transfected MCF-7-TMPTSS4 compared to its control MCF-7-NC. Moreover, TMPRSS4 silencing in breast cancer reduces cells proliferation by promoting cell cycle arrest in G2/M phase, cell apoptosis, and telomere maintenance impairment while the TMPRSS4 overexpression increases cells proliferation through cell apoptosis reduction and telomere maintenance reinforcement associated with insignificant change in cell cycle progression. Conclusion: TMPRSS4 plays important roles in cancer progression and may be considered as a good therapeutic target for cancer gene therapy especially breast cancer.