IL-29 Exhibits Anti-Tumor Effect on Pan-48 Pancreatic Cancer Cells by Up-regulation of P21 and Bax.

BACKGROUND/AIM: Pancreatic cancer is the most lethal cancer of the digestive system. IL-29 is a new member of the IFNλ family and well-known for its strong antiviral activity. However, its direct effect on pancreatic cancer is still unclear. This study was performed to investigate if IL-29 has any direct effect on Pan-48 pancreatic cancer cells. MATERIALS AND METHODS: Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the effects of IL-29 on cell survival, proliferation, and apoptosis of Pan-48 pancreatic cancer cells. RT-PCR and IHC were subsequently performed to explore IL-29's potential molecular mechanisms. RESULTS: The percentage of colonies of Pan-48 cells was decreased following the addition of IL-29. This was consistent with a decreased optical density (OD) value of cancer cells. Furthermore, the relative caspase-3 activity in cancer cells was increased after the addition of IL-29, indicating increased apoptosis of cancer cells. The anti-proliferative effect of IL-29 on cancer cells correlated with increased expression of the anti-proliferative molecule p21. The pro-apoptotic effect of IL-29 on cancer cells correlated with an increased expression of the pro-apoptotic molecule Bax. CONCLUSION: IL-29 constrains Pan-48 pancreatic cell growth via up-regulation of p21 and Bax. Our study suggests a potential use of IL-29 in immunotherapy for pancreatic cancer treatment.

Correction to: IL-39 acts as a friend to pancreatic cancer.

The original version of this article unfortunately contained a mistake in the text of the entire article. The word "IL-39" should read as "meteorin-like protein". This has been corrected with this correction.

IL-39 acts as a friend to pancreatic cancer.

Pancreatic cancer is the most lethal digestive cancer and the fourth leading cause of cancer death in the US. IL-39, a heterodimer of p19 and EBI3, is a newly found cytokine and its role in the pathogenesis of neoplasia has not been studied yet. This study was designed to investigate the direct role of IL-39 in the growth of pancreatic cancer. Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the direct effects of IL-39 on cell survival, proliferation and apoptosis of the widely studied pancreatic cancer cell line MiaPaCa-2. We further investigated the possible molecular mechanisms by using RT-PCR and IHC. The percentage of colonies of pancreatic cancer cells increased significantly in the presence of IL-39. This was paralleled with the increase in the OD value of cancer cells in the presence of IL-39. Interestingly, the relative caspase-3 activity in cancer cells decreased significantly in the presence of IL-39. Furthermore, the pro-tumor effect of IL-39 on pancreatic cancer cells correlated with decreased anti-proliferative molecule p21.The anti-apoptotic effect of IL-39 correlated with decreased pro-apoptotic molecule TRAILR1. These results suggest that IL-39 favors growth of pancreatic cancer by promoting growth and inhibiting apoptosis of cancer cells. This suggests that IL-39 acts as a friend to pancreatic cancer. Thus, inhibition of effect of IL-39 on cells might be a promising strategy to treat pancreatic cancer.

The Role of IL-37 in Non-Cancerous Diseases.

IL-37 is a newly discovered cytokine belonging to IL-1 family consisting of 11 members, which have similar ß-barrel structures and associate with Ig-like receptors. Extensive studies have been done with IL-37 since its discovery. These studies suggest that IL-37 does not only play a role in tumorigenesis, but also has anti-inflammatory properties in immune responses through the down regulation of pro-inflammatory molecules. We have previously reviewed the role of IL-37 in cancer. Here, we will focus on the role of IL-37 in non-cancerous Diseases. Such a study might be helpful to design new strategies to treat IL-37 associated diseases.

The role of IL-7 in Immunity and Cancer.

Interleukin-7 (IL-7) is a cytokine that has been known since long in immunology, mainly regarding its effects on T-cells and B-cells. IL-7 has been demonstrated to be necessary for both B-cell and T-cell proliferation and lack of IL-7 causes immature immune cell arrest. Interestingly, in recent years, certain studies have strongly suggested that the role of IL-7 is far beyond the field of immunology, it might have direct or indirect effect on cancer. This review aims to summarize the role of IL-7 in immunity and its role in the pathogenesis of neoplasia.

The novel role of IL-37 in prostate cancer: evidence as a promising radiosensitizer.

Prostate cancer (PCa) is the most common non-cutaneous cancer in men in the USA. Radiation therapy (RT) is widely considered the standard treatment for PCa. IL-37 is an IL-1 family member, and it has been extensively studied in immunity. However, no studies have been done regarding its potential as a radiosensitizer. This study is designed to investigate the direct effect of IL-37 on growth of DU145 and PC-3, two widely studied PCa cell lines, and to investigate whether IL-37 could be used as a radiosensitizer for PCa. Clonogenic survival and quick cell proliferation assays along with immunohistochemistry, TUNEL staining, and caspace-3 activity assay kits as well as RT-PCR were used in this study. Our results showed that IL-37 has little direct effect on growth of PCa. However, IL-37/RT enhanced RT-induced inhibition of cell proliferation and apoptosis in both cell lines. We further found that IL-37/RT upregulated the mRNA expression of p27, Fas, and Bax, while downregulating the mRNA expression of cdk2 in DU145 cells. These findings suggest that IL-37 has the potential to be used as a radiosensitizer for PCa and warrants further investigation.

Unveil the mysterious mask of cytokine-based immunotherapy for melanoma.

Melanoma is the leading cause of death among all skin cancers and its incidence continues to rise rapidly worldwide in the past decades. The available treatment options for melanoma remain limited despite extensive clinical research. Melanoma is an immunogenic tumor and great advances in immunology in recent decades allow for the development of immunotherapeutic agents against melanoma. In recent years, immunotherapy utilizing cytokines has been particularly successful in certain cancers and holds promise for patients with advanced melanoma. In this review, an overview of the current status and emerging perspectives on cytokine immunotherapy for melanoma are discussed in details. Such a study will be helpful to unveil the mysterious mask of cytokine-based immunotherapy for melanoma.

The role of IL-29 in immunity and cancer.

Interleukin-29 (IL-29) is a new member of the recently discovered interferon λ (IFNλ) family. It is produced predominantly by maturing dendritic cells and macrophages. It has been implicated in numerous immunological responses and has shown antiviral activity similar to the Type I interferons, although its target cell population is more limited than the Type I interferons. In recent years, the role of IL-29 in the pathogenesis of various cancers has also been extensively studied. In this review, we will discuss the recent advances of IL-29 in immunological processes and the pathogenesis of various cancer.

The role of IL-37 in cancer.

Interleukin 37 (IL-37) is a new member of the IL-1 family which all have a similar ß-barrel structure. Since its discovery, IL-37 has been studied extensively in immunological field. It has been established that IL-37 possesses anti-inflammatory characteristics both in innate immune response as well as in acquired immune responses by downregulating pro-inflammatory molecules. This review will discuss the role of IL-37 in immunological processes and neoplastic pathogenesis.