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CXCL5 knockdown attenuated gemcitabine resistance of pancreatic cancer through regulation of cancer cells and tumour stroma.


ABSTRACT: Chemoresistance is one of the major causes to the poor prognosis of pancreatic cancer (PC). Gemcitabine alone and gemcitabine-based therapies are mostly used for the treatment of PC. Gemcitabine resistance becomes the focus of chemotherapy. C-X-C motif chemokine 5 (CXCL5), a member of the C-X-C chemokine family, acts through C-X-C chemokine receptor type 2 (CXCR2). A high level of CXCL5 is associated with worse prognosis in PC patients and increased suppressive immune cell infiltration. Increased expression of CXCL5 is also found in gemcitabine-treated PC cells. To investigate the role of CXCL5 in PC response to gemcitabine, CXCL5 knockdown (KD) PC cells were generated and its effect on cancer cell response to gemcitabine in vitro and in vivo was studied. The mechanisms involved were also explored by determining the changes in the tumour microenvironment (TME) and protein profile of the CXCL5 KD cells using immune-staining and proteomic analysis. The results showed that CXCL5 expression were increased in all PC cell lines tested and in gemcitabine-resistant tumour tissue, that CXCL5 KD suppressed PC growth and sensitized PC cell response to gemcitabine and that CXCL5 KD stimulated the activation of stromal cells in TME. We conclude that CXCL5 promotes gemcitabine resistance by affecting TME and cancer cells.

SUBMITTER: Lee NH 

PROVIDER: S-EPMC10182491 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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CXCL5 knockdown attenuated gemcitabine resistance of pancreatic cancer through regulation of cancer cells and tumour stroma.

Lee Nien-Hung NH   Ma Yi Y   Ang Ching-Seng CS   Dumesny Chelsea C   Huynh Nhi N   Yang Yang Y   Wang Kai K   Nikfarjam Mehrdad M   He Hong H  

American journal of translational research 20230415 4


Chemoresistance is one of the major causes to the poor prognosis of pancreatic cancer (PC). Gemcitabine alone and gemcitabine-based therapies are mostly used for the treatment of PC. Gemcitabine resistance becomes the focus of chemotherapy. C-X-C motif chemokine 5 (CXCL5), a member of the C-X-C chemokine family, acts through C-X-C chemokine receptor type 2 (CXCR2). A high level of CXCL5 is associated with worse prognosis in PC patients and increased suppressive immune cell infiltration. Increase  ...[more]

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