The Study On Function And Mechanism Of XBP1 In The Proliferation And Apoptosis Of Human Osteosarcoma

Malignant tumors have the characteristic of immortalization,which results in the nutrition deficiencies in the local tissue.Under this condition,tumor cells can induces a series of adaptive response signaling pathways to survive.Inositol-requiring enzyme-1α(IRE1α)/X-box binding protein 1(XBP1)axis is a vital adaptive pathway of the endoplasmic reticulum(ER)stress response.The dysfunction of XBP1 associates with the tumorigenesis of various cancers.But it remains unclear in osteosarcoma(OS).In this study,the mRNA and protein expression of XBP1 of OS tissues were detected by Real time PCR and Western blot assays.The results showed that the expression of XBP1 was higher in the OS compared to that in the corresponding non-cancerous tissues.The overexpression of XBP1 was associated with advanced OS progress.The expression of XBP1 of OS cells increased greatly when exposed in the hypoxic condition for certain period.The cell function assays was tested by siRNA Intervening technique.After knockdown of XBP1,the proliferation capability of osteosarcoma was measured by cell counting kit 8 assays(CCK8),the migration and invasion capability by Transwell assays,Cell cycle and cell apoptosis by cell cycle assays and cell apoptosis assay respectively.Through these experiments,we observed that the decreased XBP1 significantly reduced cell proliferation,probably by inhibiting G2 / M phase and enhancing apoptosis of OS cells.However,the migration and invasion ability were not reduced.Subsequently in vitro molecular experiments showed that reduced XBP1 significantly reduced the expression of PI3 K and mTOR.In fact,the PI3 K / mTOR pathway was actively involved in the process of cells proliferation and differentiation.Therefore,it may indicate that XBP1 affect OS cells proliferation and growth by regulating the PI3K/mTOR pathway.Taken together,we observed that XBP1 was up-regulated and associated with OS progress.Besides,it may regulate OS cells proliferation and growth with activation of PI3K/mTOR signaling.Thus,targeting XBP1 may provide a new potential therapeutic method for OS.