IL-37 promotes cell apoptosis in cervical cancer involving Bim upregulation.

Background: Growing evidence has indicated that interleukin-37 (IL-37) is a potential anticancer molecule that mainly plays an inhibiting role in different kinds of cancers, but data for the role of IL-37 on cell apoptosis in cancers remains rare. The present study aimed to explore the role of IL-37 in cell apoptosis in cervical cancer, and the involved apoptosis-related molecules. Methods: IL-37 was overexpressed by transfecting the pIRES2-EGFP-IL-37 plasmid in HeLa and C33A cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA expression of IL-37, Bcl-2, Bax and Bim. Western blotting was performed to detect the protein expression of IL-37 and Bim. Cell apoptosis was detected by flow cytometry. Results: IL-37 upregulated the mRNA expression levels of Bim by 138.40% for HeLa (P<0.05) and 58.95% for C33A (P<0.05), and increased the protein expression levels of BimL by 69.10% (P<0.05) and 56.66% (P<0.05) in HeLa and C33A, respectively. Overexpression of IL-37 increased the apoptosis rates by 152.86% for HeLa (P<0.01) and 25.4% for C33A (P<0.05). Knockdown of Bim by specific siRNA interference fragments (SiBim) reduced the apoptosis rates by 36.00% for HeLa (P<0.05) and 14.66% for C33A (P<0.05). Compared with the IL-37 overexpression group, the apoptosis rate in cotransfecting the IL-37 overexpression plasmid and SiBim group decreased by approximately 31% (P<0.05) and 24.35% (P<0.05) in HeLa and C33A, respectively. Conclusion: IL-37 upregulated Bim in cervical cancer cells. Furthermore, IL-37 can promote cervical cancer cell apoptosis, but Bim knockdown decreased this promotion through IL-37. Thus, IL-37 can promote cervical cancer cell apoptosis, which involve the upregulation of Bim.

Interleukin 37 Expression Inhibits STAT3 to Suppress the Proliferation and Invasion of Human Cervical Cancer Cells.

OBJECTIVES: The most recently discovered cytokine interleukin 37 (IL-37) received growing attention. Its function on tumor is largely unknown. Here, we investigated the biological function of IL-37 on cervical cancer (CC). Materials and methods : HPV(+) Hela cells and HPV(-) C33A cells were used. RT-qPCR was performed to detect the transcription of IL-37, STAT3, TNF-αand IL-1ß. Western blotting was used for protein detection. CCK-8 assay and transwell assay were employed for cell proliferation and invasion detection, respectively. Results : Successful gene transfection of IL-37 suppressed the proliferation and invasion of CC. Interestingly, IL-37 showed higher anticancer ability in HPV(+) Hela cells than that in HPV(-) C33A cells. Then, the molecular mechanism of IL-37 anticancer was explored. Firstly, we found that IL-37 inhibited STAT3 expression at both mRNA and protein levels. IL-37 also down regulated the phosphorylation of STAT3. Secondly, blockage of STAT3 using siRNAs reduced significantly the ability of IL-37 to suppress cell proliferation and invasion. Thirdly, STAT3 knockdown reduced markedly the inhibition of IL-37 on the transcription of tumor-derived TNF-α and IL-1ß, indicating the contribution of STAT3 for the cancer associated antiinflammation of IL-37. Finally, STAT3 up regulation restored the ability of cell proliferation, cell invasion and the expression of inflammatory cytokines, TNF-α and IL-1ß. Conclusions : IL-37 suppressed cell proliferation and invasion of CC and STAT3 is involved in this process. Thus, IL-37 emerges as a new anticancer cytokine for CC. This study demonstrated a new biological function of IL-37 and offered a potential molecule for CC treatment.