Krüppel-like factor 4 promotes high-mobility group box 1-induced chemotherapy resistance in osteosarcoma cells.
Bottom Line: Osteosarcoma is the most common primary malignant bone tumor, and the frequent acquisition of chemoresistance is often an obstacle to achieving favorable outcomes during chemotherapy.In this study, quantitative real-time PCR and western blot analysis revealed that KLF4 expression was significantly increased in response to cisplatin, methotrexate and doxorubicin treatment in osteosarcoma cells, and knockdown of KLF4 increased sensitivity to these anticancer drugs by decreasing cellular clonogenic ability and increasing apoptosis.Moreover, our data suggest that KLF4-regulated drug resistance might, at least partially, positively regulate high-mobility group box 1 (HMGB1), which was found to be a significant contributor to chemoresistance in osteosarcoma cells in our previous study.
Affiliation: Department of Orthopaedics, The 2nd Xiangya Hospital, Central South University, Changsha, China.Show MeSH
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Mentions: To examine the potential role of KLF4 in the regulation of anticancer drug sensitivity of osteosarcoma cells, we established KLF4 knocked down osteosarcoma cells by KLF4‐specific siRNA (MG‐63/si‐KLF4, SaOS‐2/si‐KLF4) and the corresponding control cells by scrambled siRNA (MG‐63/si‐Con and SaOS‐2/si‐Con). qRT‐PCR and western blot analysis validated that MG‐63/si‐KLF4 and SaOS2/si‐KLF4 cells expressed significantly lower mRNA and protein levels of KLF4 than in the corresponding control cells. Using the MTT assays, we found that knockdown of KLF4 in these cells rendered them significantly more sensitive to Dox‐induced, Cis‐induced and Mtx‐induced cell injury, respectively (Fig. 2a), and this was also associated with drastically decreased clonogenic ability (Fig. 2b) and high levels of apoptotic cell death (Fig. 2c). In contrast, when KLF4 was overexpressed in MG‐63 and SaOS‐2 cells, we observed an opposite effect on Dox‐induced, Cis‐induced and Mtx‐induced cell injury (Fig. 3a), clonogenic ability (Fig. 3b) and apoptotic cell death (Fig. 3c). Taken together, these data suggest that targeted suppression of KLF4 increases sensitivity to chemotherapy in osteosarcoma cells in vitro.
Affiliation: Department of Orthopaedics, The 2nd Xiangya Hospital, Central South University, Changsha, China.