Low Expression of Smurf1 Enhances the Chemosensitivity of Human Colorectal Cancer to Gemcitabine and Cisplatin in Patient-Derived Xenograft Models |
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Affiliation: | 1. Beijing Municipal Key Laboratory of Advanced Energy Materials and Technology, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China;2. Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Beijing 100021, China;3. Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, 101 Stephenson Parkway, Norman, OK 73019-5300, USA;4. Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing 100021, China;5. Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China |
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Abstract: | Despite the side effects, chemotherapy is one of the most common treatments in colorectal cancer (CRC). An open-ended question about CRC chemotherapy, which has been discussed quite often, is with respect to the validation of prognostic or predictive factors. It is believed that personalized chemotherapy can improve the treatment outcome of patients with colorectal tumors. Though, Smurf1 is highly expressed in multiple tumors and plays a critical role in the occurrence and development of multiple cancers, it’s role in the susceptibility of CRC response to chemotherapy is still unknown, Therefore, the study aimed to understand the role of Smurf1 in the susceptibility of CRC response to chemotherapy. The study showed that the knockdown of Smurf1 increases gemcitabine and cisplatin-induced HCT116 cells apoptosis in vitro. Furthermore, in vivo experiments showed that tumors that had low Smurf1 expression exhibited enhanced gemcitabine, cisplatin, and gemcitabine plus cisplatin anti-tumor effects in HCT116 cell-derived xenograft (CDX) models and patient-derived xenograft (PDX) models. In conclusion, the results indicated that Smurf1 inhibits the chemosensitivity of CRC to gemcitabine, cisplatin, and gemcitabine plus cisplatin. Therefore, downregulati1ng the Smurf1 expression is a potential strategy to increase the efficacy of gemcitabine and cisplatin in CRC patients. |
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