CXCL12 modulates the radiosensitivity of cervical cancer by regulating CD44

Abstract

The aim of the present study was to investigate the regulation of stromal cell-derived factor 1 (CXCL12) in the radioresistance of cervical cancer, which was upregulated in tumors in our previous study. A CCK-8 assay was used to detect cell viability. Flow cytometry was used to measure cell apoptosis and the expression levels of CD44 and CXCR4. ELISA was performed to measure the expression level of CXCL12 protein and CXCL12 mRNA was detected by reverse transcription-quantitative polymerase chain reaction assays. Cell viability and apoptosis were determined with or without treatment with CXCL12 small interfering (si)RNA to examine the function of CXCL12 in Hela cells. The expression level of CD44 antigen (CD44) and C-X-C chemokine receptor type 4 (CXCR4) were measured using flow cytometry in the presence of CXCL12 and irradiation. In the present study, it was demonstrated that inhibition of CXCL12 reduced cell viability and increased cellular apoptosis in Hela cells treated with irradiation. Following treatment with CXCL12 siRNA, the expression level of CD44 was downregulated and the expression level of CXCR4 was upregulated. This effect of regulation additionally occurred in the presence of irradiation. In conclusion, the present data demonstrated that CXCL12 served an important role in the radioresistance of cervical cancer, suggestinh a novel therapeutic target.

The Role of Chemokines in Cervical Cancers

“…After treatment with CXCL12 siRNA in the same cell culture model, the expression level of CD44 was downregulated and the expression level of CXCR4 was upregulated [77]. The regulation effect that is described above also occurred during irradiation [77]. Another in vitro study used plerixafor in combination to radio/chemotherapy and the combined treatmentinduced increases in the CXCL12/CXCR4 signaling [78].…”

“…An in vitro study with Hela cells showed that inhibition of CXCL12 decreased cell viability and increased cellular apoptosis in radiation-treated cells [77]. After treatment with CXCL12 siRNA in the same cell culture model, the expression level of CD44 was downregulated and the expression level of CXCR4 was upregulated [77].…”

Drug Delivery Systems in the Development of Novel Strategies for Glioblastoma Treatment

“…The CXCL12/CXCR4 axis has gained increased focus during the recent decade [107] and has been extensively studied in brain tumors (GBM, astrocytoma, medulloblastoma, oligodendroglioma, and oligodendroastrocytoma) [108] due to its key role in the communication of tumor cells with their microenvironment [109]. The axis is implicated in GBM immunosuppression, chemotherapy and radiotherapy resistance [107,110], cellular reprogramming, and ECM remodeling [107]. CXCL12 acts primarily via two mechanisms in cancer: (a) through an autocrine effect that promotes cancer cell growth, invasion, and angiogenesis, and (b) indirectly by recruiting cancer cells expressing CXCR4 into regions or organs containing CXCL12 to initiate metastasis [111].…”

miR‐122‐5p modulates the radiosensitivity of cervical cancer cells by regulating cell division cycle 25A (CDC25A)

“…Unfortunately, radiotherapy and chemotherapy are not effective in some cases, and the 5‐year survival rate of this disease is only 40–50% . Even more serious, it has been increasingly reported that some tumor cells have reduced sensitivity to X‐rays, and the treatment effect for patients with cervical cancer is far from meeting our expectations . Therefore, it is urgent to explore the mechanism of radiation resistance of cervical cancer cells and improve the prognosis of patients.…”