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      p53 overexpression increases chemosensitivity in multidrug resistant osteosarcoma cell lines

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          Abstract

          Purpose

          Multidrug resistance (MDR) is a major obstacle to the successful treatment of osteosarcoma with chemotherapy. Effectiveness of cancer therapy correlates with the ability to induce a p53-dependent apoptotic response. p53 is a tumor suppressor gene that is mutated in 22% of osteosarcomas. While impaired p53 has been implicated in the oncogenesis of osteosarcoma, it is unclear whether overexpression of wild type p53 can increase chemosensitivity in MDR osteosarcoma cells.

          Methods

          We transfected a plasmid encoding the wild type p53 gene to MDR osteosarcoma cell lines, which have different p53 statuses, U-2OSR2 with wild type p53 (Wt-p53) and KHOSR2 with mutant p53 (Mt-p53), and determined the effect of p53 overexpression on chemosensitivities.

          Results

          Both of the U-2OSR2 and KHOSR2 cell lines displayed similar trends in p53 induced drug sensitivities. However, it seems that the impact of p53 overexpression is different based on the differential intrinsic p53 status in these cell lines. In the KHOSR2 cell line (Mt-p53), overexpression of p53 up-regulates the expression of pro-apoptotic protein p21 and Bax, while in the U-2OSR2 cell line (Wt-p53), overexpression of p53 down-regulates IGF-1r expression significantly.

          Conclusions

          These results demonstrated that tansfection of wild type p53 increases chemosensitivity through inhibiting either IGF-1r or through increasing the expression of pro-apoptotic proteins p21 and Bax in human MDR osteosarcoma cell lines.

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          Author and article information

          Journal
          7806519
          2664
          Cancer Chemother Pharmacol
          Cancer Chemother. Pharmacol.
          Cancer chemotherapy and pharmacology
          0344-5704
          1432-0843
          29 December 2015
          23 December 2015
          February 2016
          01 February 2017
          : 77
          : 2
          : 349-356
          Affiliations
          [a ]Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, 02114 MA, United States
          [b ]Department of Orthopedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
          Author notes
          [* ] Corresponding author address: Zhenfeng Duan, Massachusetts General Hospital, Center for Sarcoma and Connective Tissue Oncology, 100 Blossom St., Jackson 1115, Boston, MA 02114, Tel: +1 617-724-3144, Fax: +1 617-726-3883, zduan@ 123456mgh.harvard.edu
          Article
          PMC4749432 PMC4749432 4749432 nihpa747512
          10.1007/s00280-015-2944-z
          4749432
          26698867
          8d285243-2720-451e-9313-ff0a651ff156
          History
          Categories
          Article

          Osteosarcoma,MDR,p53,Apoptosis
          Osteosarcoma, MDR, p53, Apoptosis

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