SiRNA interfering STAT3 enhances DDP sensitivity in cervical cancer cells

L.-L. Huang, W. Rao

Department of Gynecology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China. tuanduliao@163.com

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• Oncology

OBJECTIVE: Signal transducer and activator of transcription 3 (STAT3) is an important regulatory protein in the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, which regulates cell proliferation, apoptosis, and other biological processes. It is closely related to tumor occurrence, progress, and resistance. Cisplatin (DDP) resistant cervical cancer cell line was established by shock induction to investigate the role of STAT3 in cervical cancer cells drug resistance.

PATIENTS AND METHODS: The expression of STAT3 in different chemotherapy response cervical cancer tissues was compared. The cervical cancer was divided into two groups upon STAT3 median level. Cervical cancer cell inhibitory rate by DDP treatment was compared. Western blot was used to detect STAT3 and phosphorylated STAT3 (p-STAT3) expressions in CaSki and CaSki/DDP cells. Cell apoptosis rate was tested by flow cytometry. CaSki/DDP cells were divided into small interfere RNA-normal control (siRNA-NC) group and siRNA-STAT3 group. Cell proliferation was evaluated by EdU staining.

RESULTS: The rate of STAT3 over-expression in cervical cancer patients with no significant chemotherapy response was markedly higher than that with a significant response. The inhibitory effect of DDP on tumor cells derived from patients with low STAT3 expression was significantly higher, while the apoptosis rate was apparently lower than that of CaSki/DDP cells from patients with high STAT3 expression. siRNA-STAT3 transfection significantly reduced the expressions of STAT3 and p-STAT3, decreased cell proliferation, and enhanced cell apoptosis in CaSki/DDP cells.

CONCLUSIONS: STAT3 over-expression is associated with DDP resistance in cervical cancer. Decreasing STAT3 can significantly promote the apoptosis of cervical cancer CaSki cells and decrease the DDP resistance.

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