Hematological Effects, Serum, and Pulmonary Cytokine Profiles in a Melanoma Mouse Model Treated with GK1.

Abstract

OBJECTIVE:

In a previous study, we demonstrated the therapeutic efficacy of a subcutaneous injection of GK1 peptide in a melanoma mouse model, effectively increasing the mean survival time by 42.58%, delaying tumor growth, and increasing intratumoral necrosis compared with the control. As a first approach to investigate the anti-melanoma effect of GK1, this study was carried out to determine the hematological effects along with both serum and lung cytokine profiles in a melanoma lung metastatic model.

MATERIALS AND METHODS:

Thirteen C57BL6 female mice were transfected in the lateral tail vein with 2×10(5) B16-F0 melanoma cells. After 7 days, mice were separated in two different groups and treatments were initiated (day 0): The GK1-treated group (seven mice) were injected every 5 days intravenously with GK1 (10 μg) in the lateral tail vein, and the control group (six mice) were injected every 5 days with intravenous saline solution. Blood samples were collected every 5 days from day 0; tumor samples were obtained for cytokine measurements on the day of sacrifice.

RESULTS:

In the peripheral blood, mice treated with GK1 presented a statistically significant decrease in IFN-γ (p<0.05), and lymphocytes tended to be lower compared with the control mice (p=0.06). Lung metastatic analysis demonstrated a significant increase in IFN-γ and IL-12p70 (p<0.05); a significant decrease in IL-17, IL-4, IL-22, IL-23, and IL-12p40 (p<0.05); and a marginal decrease in IL-1β (p=0.07) compared with the control.

DISCUSSION:

Our results suggest that an intratumoral increase of cytokines with antitumor activity along with an intratumoral decrease of cytokines with protumor activity could explain, in part, the anti-melanoma effects of GK1 in a lung metastatic melanoma mouse model. Further studies must be performed to elucidate the precise mechanisms of action for GK1 peptide against melanoma, and their eventual application in humans.

• Authors: Armando Pérez-Torres, Jesus Vera-Aguilera, Jorge H Sahaza, Carlos Vera-Aguilera, Eduardo Moreno-Aguilera, Evelyn Pulido-Camarillo, Luis Nuñez-Ochoa, Pratheepa Jeganathan
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 30 Issue 6 Pg. 247-54 (Aug 2015) ISSN: 1557-8852 [Electronic] United States
• PMID: 26181852 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines

Topics

• Animals
• Cytokines (genetics)
• Disease Models, Animal
• Female
• Humans
• Immunotherapy
• Lung Neoplasms (genetics)
• Melanoma, Experimental (genetics, pathology)
• Mice
• Mice, Inbred C57BL