CXCR4 enhances cisplatin resistance of human tongue squamous cell carcinoma.
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Carcinoma, Squamous Cell
/ genetics
Caspase 3
/ metabolism
Cell Proliferation
Cisplatin
/ pharmacology
Cyclin D1
/ metabolism
Drug Resistance, Neoplasm
/ genetics
Gene Silencing
Humans
RNA, Small Interfering
Receptors, CXCR4
/ physiology
Tongue Neoplasms
/ genetics
Tumor Cells, Cultured
bcl-2-Associated X Protein
/ metabolism
CXCR4
chemotherapy resistance
proliferation and apoptosis
tongue squamous cell carcinoma
Journal
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
ISSN: 1600-0714
Titre abrégé: J Oral Pathol Med
Pays: Denmark
ID NLM: 8911934
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
received:
11
08
2018
revised:
01
12
2018
accepted:
10
12
2018
pubmed:
17
12
2018
medline:
29
5
2019
entrez:
17
12
2018
Statut:
ppublish
Résumé
The chemokine receptor 4 (CXCR4) plays an important role in tumor progression. Overexpressed CXCR4 is associated with a poor prognosis of patient with head and neck squamous cell carcinomas. However, the correlation between CXCR4 and chemotherapy resistance in tongue squamous cell carcinoma (TSCC) remains obscure. Stable cisplatin-resistant CAL27 CDDP and SCC25 CDDP cells were established and identified by CCK8 assay, and the CXCR4 expression was detected using qRT-PCR and Western blot. CXCR4-siRNA was transfected into TSCC CDDP cells, whose transfect efficiency was examined. Cisplatin sensitivity was further detected, as well as several proliferation and apoptosis-related proteins. CAL27 CDDP and SCC25 CDDP cells were successfully established, which exhibited significantly higher cell viability and less apoptosis under cisplatin stimulation than that of parental cells. CXCR4 expression was increased in TSCC CDDP cells. After transfection of CXCR4-siRNA, the expression of CXCR4 was reduced by 73% and 78% in CAL27 CDDP and SCC25 CDDP cells, respectively. CCK8 assay and flow cytometry assay revealed that the proliferative capacity under cisplatin stimulation significantly decreased after CXCR4 silencing. Moreover, increased TSCC CDDP cells were arrested in the G0/G1 phase after knockdown of CXCR4. Compared with negative control group, the expression of cyclin D1 and p-AKT decreased, while that of p-caspase-3 and Bax significantly increased. Silencing CXCR4 may evidently inhibit proliferation, induce apoptosis and enhance cisplatin sensitivity of TSCC CDDP cells by reduced cyclin D1 and p-AKT, and increased p-caspase-3 and Bax.
Sections du résumé
BACKGROUND
BACKGROUND
The chemokine receptor 4 (CXCR4) plays an important role in tumor progression. Overexpressed CXCR4 is associated with a poor prognosis of patient with head and neck squamous cell carcinomas. However, the correlation between CXCR4 and chemotherapy resistance in tongue squamous cell carcinoma (TSCC) remains obscure.
METHODS
METHODS
Stable cisplatin-resistant CAL27 CDDP and SCC25 CDDP cells were established and identified by CCK8 assay, and the CXCR4 expression was detected using qRT-PCR and Western blot. CXCR4-siRNA was transfected into TSCC CDDP cells, whose transfect efficiency was examined. Cisplatin sensitivity was further detected, as well as several proliferation and apoptosis-related proteins.
RESULTS
RESULTS
CAL27 CDDP and SCC25 CDDP cells were successfully established, which exhibited significantly higher cell viability and less apoptosis under cisplatin stimulation than that of parental cells. CXCR4 expression was increased in TSCC CDDP cells. After transfection of CXCR4-siRNA, the expression of CXCR4 was reduced by 73% and 78% in CAL27 CDDP and SCC25 CDDP cells, respectively. CCK8 assay and flow cytometry assay revealed that the proliferative capacity under cisplatin stimulation significantly decreased after CXCR4 silencing. Moreover, increased TSCC CDDP cells were arrested in the G0/G1 phase after knockdown of CXCR4. Compared with negative control group, the expression of cyclin D1 and p-AKT decreased, while that of p-caspase-3 and Bax significantly increased.
CONCLUSIONS
CONCLUSIONS
Silencing CXCR4 may evidently inhibit proliferation, induce apoptosis and enhance cisplatin sensitivity of TSCC CDDP cells by reduced cyclin D1 and p-AKT, and increased p-caspase-3 and Bax.
Substances chimiques
Antineoplastic Agents
0
BAX protein, human
0
CXCR4 protein, human
0
RNA, Small Interfering
0
Receptors, CXCR4
0
bcl-2-Associated X Protein
0
Cyclin D1
136601-57-5
Caspase 3
EC 3.4.22.-
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
122-128Subventions
Organisme : National Natural Science Foundation of China
ID : 81600899
Organisme : National Natural Science Foundation of China
ID : 81702695
Informations de copyright
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.