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Du Meng,1,* Hongwei Lei,2,* Xiaoqiang Zheng,3 Yaxuan Han,4 Ronggang Sun,5 Dongli Zhao,1 Rui Liu11Department of Radio Oncology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, 710061, People’s Republic of China; 2Department of Radio Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116027, People’s Republic of China; 3Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, 710061, People’s Republic of China; 4Department of Oncology, The Xi’an Chest Hospital, Xi’an, Shaanxi Province, 710000, People’s Republic of China; 5Department of Radio Oncology, The People’s Hospital of YangZhong City, YangZhong, Jiangsu Province, 212200, People’s Republic of China*These authors contributed equally to this workBackground: Breast cancer is one of the foremost threats to female health nowadays. Tamoxifen, an antagonist of estrogen receptor-α (ERα), is the first choice for endocrine-dependent breast cancer (ERα-positive breast cancer) treatment. However, ERα has an important function in the normal physical regulation of estrogen, and current oral administration of tamoxifen has potential side effects on normal endocrine secretion. In the present work, we aim to develop novel approaches to increase the antitumor effect of tamoxifen on breast cancer cells and decrease the potential side effects in the human body during treatment.Methods: A temperature-sensitive phase-change hydrogel for tamoxifen (Tam-Gel) was generated. After establishing subcutaneous tumors formed by MCF-7, an ERα-positive breast cancer cell line, in nude mice, an intratumoral injection of Tam-Gel was performed to examine whether Tam-Gel facilitated the slow-release or

Du Meng,1,* Ming Lei,2,* Yaxuan Han,3 Dongli Zhao,2 Xiaozhi Zhang,1 Yunyi Yang,1 Rui Liu1 1Department of Radio Oncology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an 710061, Shaanxi Province, People’s Republic of China; 2Department of Cardiothoracic Surgery, The NO 3 Hospital of Xi’an, Xi’an 710000, Shaanxi Province, People’s Republic of China; 3Department of Oncology, The Xi’an Chest Hospital, Xi’an 710000, Shaanxi Province, People’s Republic of China *These authors contributed equally to this work Background: Urokinase plasminogen activator (uPA) promotes the in vivo invasive growth of HCC cells by cleaving and activating matrix metalloproteinases (MMPs) to induce the destruction of the extracellular matrix of triple-negative breast cancer (TNBC) cells. The identification of microRNAs that target uPA and decrease uPA expression would be useful for attenuating the in vivo invasive growth of TNBC cells.Materials and methods: MicroRNA-645 (miR-645) was identified using an online tool (miRDB) as potentially targeting uPA; miR-645 inhibition of uPA was confirmed by western blot experiments. The effects of miR-645 on the in vivo invasive growth of TNBC cells were examined using an intrahepatic tumor model in nude mice, and the miR-645 mechanism of action was explored with MMP cleaving experiments.Results: Through virtual screening, we discovered that miR-645 potentially targeted the uPA 3' untranslated region. This targeting was confirmed by western blot experiments and miR-645 lentiviral particle (LV-645) transduction that inhibited uPA expression in MDA-MB-231 TNBC cells. The LV-645 inhibition of uPA led to the decreased invasive growth of TNBC cells in nude mice. The mechanism data indicated that the uPA inhibition resulted in a decreased cleaving of the pro-MMP-9 protein.Conclusion: Targeting uPA with miR-645 decreased the in vivo