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Krüppel-like factor 4 promotes high-mobility group box 1-induced chemotherapy resistance in osteosarcoma cells.

Huang J, Liu K, Song D, Ding M, Wang J, Jin Q, Ni J - Cancer Sci. (2016)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics, The 2nd Xiangya Hospital, Central South University, Changsha, China.

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Krüppel‐like factor 4 (KLF4) positively regulates high‐mobility group box 1 (HMGB1) expression in osteosarcoma cells. (a,b) KLF4 was overexpressed by transfecting with KLF4 expression plasmids (pcDNA3.1‐KLF4) or knocked down by KLF4‐specific siRNA (si‐KLF4) in MG‐63 and SaOS‐2 cells, and qRT‐PCR was performed to validate the KLF4 mRNA levels. (c) The expression levels of KLF4 as well as HMGB1 protein were examined by western blot, which revealed that KLF4 positively regulates HMGB1 expression in osteosarcoma cells. *P < 0.05 versus the control.
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cas12864-fig-0004: Krüppel‐like factor 4 (KLF4) positively regulates high‐mobility group box 1 (HMGB1) expression in osteosarcoma cells. (a,b) KLF4 was overexpressed by transfecting with KLF4 expression plasmids (pcDNA3.1‐KLF4) or knocked down by KLF4‐specific siRNA (si‐KLF4) in MG‐63 and SaOS‐2 cells, and qRT‐PCR was performed to validate the KLF4 mRNA levels. (c) The expression levels of KLF4 as well as HMGB1 protein were examined by western blot, which revealed that KLF4 positively regulates HMGB1 expression in osteosarcoma cells. *P < 0.05 versus the control.

Mentions: Our previous report revealed that chemotherapy agents, including Cis, Mtx and Dox, induced HMGB1 expression in osteosarcoma cells.16 To determine whether KLF4 is responsible for HMGB1 transcriptional regulation, we examined the effect of KLF4 knockdown or overexpression on the expression of HMGB1 in MG‐63 and SaOS‐2 cells. qRT‐PCR and western blot analysis both revealed that knockdown of KLF4 inhibited mRNA and protein expression levels of HMGB1 in MG‐63 and SaOS‐2 cells, while overexpression of KLF4 resulted in increased HMGB1 expression (Fig. 4). This suggests that KLF4 may positively regulate HMGB1 expression in osteosarcoma cells.


Krüppel-like factor 4 promotes high-mobility group box 1-induced chemotherapy resistance in osteosarcoma cells.

Huang J, Liu K, Song D, Ding M, Wang J, Jin Q, Ni J - Cancer Sci. (2016)

Krüppel‐like factor 4 (KLF4) positively regulates high‐mobility group box 1 (HMGB1) expression in osteosarcoma cells. (a,b) KLF4 was overexpressed by transfecting with KLF4 expression plasmids (pcDNA3.1‐KLF4) or knocked down by KLF4‐specific siRNA (si‐KLF4) in MG‐63 and SaOS‐2 cells, and qRT‐PCR was performed to validate the KLF4 mRNA levels. (c) The expression levels of KLF4 as well as HMGB1 protein were examined by western blot, which revealed that KLF4 positively regulates HMGB1 expression in osteosarcoma cells. *P < 0.05 versus the control.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814257&req=5

cas12864-fig-0004: Krüppel‐like factor 4 (KLF4) positively regulates high‐mobility group box 1 (HMGB1) expression in osteosarcoma cells. (a,b) KLF4 was overexpressed by transfecting with KLF4 expression plasmids (pcDNA3.1‐KLF4) or knocked down by KLF4‐specific siRNA (si‐KLF4) in MG‐63 and SaOS‐2 cells, and qRT‐PCR was performed to validate the KLF4 mRNA levels. (c) The expression levels of KLF4 as well as HMGB1 protein were examined by western blot, which revealed that KLF4 positively regulates HMGB1 expression in osteosarcoma cells. *P < 0.05 versus the control.
Mentions: Our previous report revealed that chemotherapy agents, including Cis, Mtx and Dox, induced HMGB1 expression in osteosarcoma cells.16 To determine whether KLF4 is responsible for HMGB1 transcriptional regulation, we examined the effect of KLF4 knockdown or overexpression on the expression of HMGB1 in MG‐63 and SaOS‐2 cells. qRT‐PCR and western blot analysis both revealed that knockdown of KLF4 inhibited mRNA and protein expression levels of HMGB1 in MG‐63 and SaOS‐2 cells, while overexpression of KLF4 resulted in increased HMGB1 expression (Fig. 4). This suggests that KLF4 may positively regulate HMGB1 expression 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedics, The 2nd Xiangya Hospital, Central South University, Changsha, China.

Show MeSH
Related in: MedlinePlus