Exogenous HMGB1 Promotes the Proliferation and Metastasis of Pancreatic Cancer Cells
Research Square (Research Square)(2020)
摘要
Abstract Backgroud: Exogenous HMGB1 play a vital role in tumor recurrence,which reside in the tumor microenvironment. However, the mechanism of action is still unknow. We studied the proliferation and metastasis effect of exogenous HMGB1 on human SW1990 and Panc-1 cells after radiotherapy and explored the possible molecular mechanism.Materials and Methods: Residual Panc-1 cells and SW1990 cells were isolated after radiotherapy. The supernatant after radiotherapy was collected. The relative expression of HMGB1 was evaluated by Enzyme Linked Immunosorbent Assay (ELISA). The images of normal pancreatic cancer cells and residual pancreatic cancer cells were collected by Electron microscope (EMS). The proliferation of pancreatic cancer cells which were treated with difference groups was measured by Carboxy fluorescein succinimidylester (CFSE). The migration rates were measured by wound healing assays. The expression of related proteins were detected by Western Blot. In vivo, the subcutaneous pancreatic tumor models of nude mice were created and therapeutic capabilities were tested.Results: HMGB1 was found in the supernatant of pancreatic cancer cells after radiotherapy. The results of CFSE showed that exogenous HMGB1 could promote the proliferation of pancreatic cancer cells. Meanwhile, HMGB1 also could promote the metastasis of PC cells. By western blot, HMGB1 could upregulation of p-GSK 3β, N-CA, Bcl-2, and Ki67 and down-regulation of E-CA. In vivo, EP (HMGB1 inhibitor) could inhibit the growth of tumors and HMGB1 could promote the proliferation of tumors post-radiotherapy.Conclusion: Radiotherapy could induce HMGB1 released into extracellular. Exogenous HMGB1 could promote the proliferation and metastasis of Panc-1 cells and SW1990 cells by upregulating p-GSK 3β expression which might depend on Wnt pathway.
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关键词
pancreatic cancer,metastasis
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