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CXCR‐4 knockdown by small interfering RNA inhibits cell proliferation and invasion of oral squamous cell carcinoma cells
Author(s) -
Hong JiSoo,
Pai HyunKyung,
Hong KyoungOk,
Kim MiAe,
Kim JiHong,
Lee JaeIl,
Hong SamPyo,
Hong SeongDoo
Publication year - 2009
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2008.00671.x
Subject(s) - downregulation and upregulation , gene knockdown , small interfering rna , cell growth , cancer research , biology , cell , cell culture , transfection , biochemistry , gene , genetics
Background: Oral squamous cell carcinomas (OSCCs) are characterized by a high degree of local invasion and a high rate of metastases to cervical lymph nodes. Downregulation of CXCR‐4 by siRNA inhibits invasion and growth of breast and colon cancer cells. However, there have been no reports on the downregulation of CXCR‐4 by small interfering RNA (siRNA) in oral cancer cells. Methods: We generated two stable CXCR‐4‐knockdown clones (KBsi and KOSCC‐25Bsi) from the KB and KOSCC‐25B OSCC cell lines by lentiviral delivery. In vitro invasion and cell proliferation assays were used to investigate the effect of CXCR‐4 downregulation on cell proliferation and invasiveness in KBsi and KOSCC‐25Bsi. Immunohistochemistry was performed to evaluate the correlation between CXCR‐4 expression and proliferation in 26 OSCC tissue samples. Results: CXCR4‐knockdown OSCC cells showed reduced invasiveness. The invasiveness of KBsi decreased to 29.5% of the vector‐infected controls, and KOSCC‐25Bsi decreased to 38.1% of the control vector‐infected cells ( P < 0.05). The CXCR4‐knockdown OSCC cells grew significantly slower than the vector‐infected control cells. KBsi and KOSCC‐25Bsi cells proliferated at 69.5% and 71.7%, respectively, of the rate of control vector‐infected cells ( P < 0.05). CXCR‐4‐positive group had significantly higher PCNA labeling index than CXCR‐4‐negative group in OSCC tissue samples. Conclusion: These results suggest that the downregulation of CXCR‐4 induces anti‐proliferative and anti‐invasive effects in OSCC and that CXCR‐4 might be a useful target molecule for the treatment of OSCC.