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TIPE2 sensitizes osteosarcoma cells to cis-platin by down-regulating MDR1 via the TAK1- NF-κB and - AP-1 pathways

Peiqing Zhao1, Sujie Wang2, Jie Jiang3

  • 1Department of Gynecologic Oncology, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China; Center of Translational Medicine, Zibo Central Hospital, Zibo, China.

Molecular Immunology
|August 17, 2018
PubMed

Insights

Tumor suppressor TIPE2 (TIPE2) is downregulated in cisplatin-resistant osteosarcoma, increasing MDR1 expression. Restoring TIPE2 sensitizes osteosarcoma cells to cisplatin by inhibiting MDR1, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • TIPE2 (TIPE2) is implicated in various cancers.
  • The role of TIPE2 in osteosarcoma chemoresistance remains unclear.
  • Multidrug resistance 1 (MDR1) is a key factor in chemotherapy failure.

Purpose of the Study:

  • To investigate the mechanism of TIPE2 in cisplatin resistance in osteosarcoma.
  • To determine the relationship between TIPE2 and MDR1 expression in osteosarcoma.

Main Methods:

  • Analysis of TIPE2 and MDR1 expression in cisplatin-resistant osteosarcoma tissues and cell lines.
  • In vitro and in vivo experiments involving TIPE2 overexpression.
  • Investigation of the regulatory pathways (TAK1-NF-κB and -AP-1) involved in MDR1 transcription.

Main Results:

  • TIPE2 expression was decreased, while MDR1 expression was increased in resistant osteosarcoma.
  • Overexpression of TIPE2 inhibited MDR1 expression and enhanced cisplatin sensitivity.
  • TIPE2 suppressed MDR1 transcription by interfering with TAK1-NF-κB and -AP-1 signaling pathways.

Conclusions:

  • TIPE2 sensitizes osteosarcoma cells to cisplatin by downregulating MDR1.
  • TIPE2 acts as a tumor suppressor in osteosarcoma chemoresistance.
  • TIPE2 represents a potential therapeutic target for overcoming cisplatin resistance in osteosarcoma.
Keywords:
Cis-platinMDR1OsteosarcomaTAK1TIPE2

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