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Int Immunopharmacol ; 136: 112377, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38838554

RESUMO

The tumor microenvironment (TME) concept has been proposed and is currently being actively studied. The development of extracellular matrix (ECM) in the TME is known as desmoplasia and is observed in many solid tumors. It has also been strongly associated with poor prognosis and resistance to drug therapy. Recently, cellular senescence has gained attention as an effect of drug therapy on cancer cells. Cellular senescence is a phenomenon wherein proliferating cells become resistant to growth-promoting stimuli, secrete the SASP (senescence-associated phenotypic) factors, and stably arrest the cell cycle. These proteins are rich in pro-inflammatory factors, such as interleukin (IL)-6, IL-8, C-X-C motif chemokine ligand 1, C-C motif chemokine ligand (CCL)2, CCL5, and matrix metalloproteinase 3. This study aimed to investigate the desmoplasia-like changes in the TME before and after cancer drug therapy in oral squamous cell carcinomas, evaluate the effect of anticancer drugs on the TME, and the potential involvement of cancer cell senescence. Using a syngeneic oral cancer transplant mouse model, we confirmed that cis-diamminedichloroplatinum (II) (CDDP) administration caused desmoplasia-like changes in cancer tissues. Furthermore, CDDP treatment-induced senescence in tumor-bearing mouse tumor tissues and cultured cancer cells. These results suggest CDDP administration-induced desmoplasia-like structural changes in the TME are related to cellular senescence. Our findings suggest that the administration of anticancer drugs alters the TME of oral cancer cells. Additionally, oral cancer cells undergo senescence, which may influence the TME through the production of SASP factors.


Assuntos
Antineoplásicos , Senescência Celular , Cisplatino , Neoplasias Bucais , Fenótipo Secretor Associado à Senescência , Microambiente Tumoral , Animais , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Cisplatino/farmacologia , Humanos , Senescência Celular/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camundongos , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Citocinas/metabolismo , Masculino , Feminino
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