CXCR4 enhances cisplatin resistance of human tongue squamous cell carcinoma

Abstract

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

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

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

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.

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