LPS Enhances the Chemosensitivity of Oxaliplatin in HT29 Cells via GSDMD-Mediated Pyroptosis
| Autor: | Bin Xu, Yi Dong, Peng Kong, Xiao-Wei Wang, Yu Song, Shuang Liu, Li Sha Wu, Mei Han, Yabin Liu, Yan Ling Lin, Jin Lai Liu, Bing Hui Li, Xiang Jie Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Programmed cell death medicine.diagnostic_test Colorectal cancer business.industry Pyroptosis medicine.disease medicine.disease_cause Gene expression profiling 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Western blot Annexin 030220 oncology & carcinogenesis medicine Cancer research Immunohistochemistry Carcinogenesis business |
| Zdroj: | Cancer Management and Research. 12:10397-10409 |
| ISSN: | 1179-1322 |
| DOI: | 10.2147/cmar.s244374 |
| Popis: | Introduction Pyroptosis induced by lipopolysaccharide (LPS) is a dissolved form of cell death. The molecular marker gasdermin D, specifically GSDMD-N, is critically required for the induction of pyroptosis. Recently, there have been studies showing that LPS is closely related to tumor biology. Methods Specimens from 40 patients with colorectal cancer (CRC) were collected. Eight- to twelve-week-old C57BL6 male mice (n=30) were raised. Immunohistochemistry and Western blot were performed to test the expression of GSDMD. Moreover, cytotoxicity assay, IL-18 and IL-1β ELISA, Annexin V and PI stain, and wound healing assay were also made. Gene Expression Profiling Interactive Analysis (GEPIA) was used to verify the expression of GSDMD and overall survival of CRC patients with a high/low expression of GSDMD. Results In the research, we showed that the poor prognosis in CRC patients was significantly related to the GSDMD expression and significantly down-regulated in human colorectal cancer (CRC) tissues. Treatment with LPS, but not TNF-α, induced pyroptosis via promoting the expression of GSDMD and GSDMD-N membrane translocation and enhanced chemosensitivity in response to L-OHP in HT29 cells. Furthermore, the enforced expression of GSDMD in HT29 cells reduced cell survival and induced cell death. Discussion These results of studies suggest that the low expression of GSDMD correlates with a poor CRC prognosis, and that pyroptosis induced by LPS may improve the anti-cancer effect of L-OHP, inhibiting the tumorigenesis of CRC by activating GSDMD. Our findings lay the foundation for further development of GSDMD serving as an important prognostic biomarker and a valid CRC therapeutic target. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|