GLUT5 increases fructose utilization in ovarian cancer

Abstract

Background: Fructose is one of the most common dietary carbohydrates in the whole world, and recent studies have found that fructose consumption is closely related to the oncogenesis and development of tumors, however, very few studies have focused on the fructose in ovarian cancer. GLUT5 (Glucose transporter type 5), as a specific fructose transporter in mammalian cells, has also been found highly expressed in many cancers. Methods: In this study, we investigated the abilities of proliferation, colony formation, and migration of ovarian cancer cells in fructose medium, and then silenced GLUT5 in ovarian cancer cells to explore the role GLUT5 in fructose metabolism in ovarian cancer. Results: The results showed that the ovarian cancer cells had similar abilities of proliferation and migration in fructose medium and glucose medium, but silencing GLUT5 could significantly inhibit these abilities in fructose medium. Meanwhile, we found that GLUT5 was higher expressed in ovarian cancer tissues, and its expression correlated significantly with tumor malignancy and poor survival of ovarian cancer patients. Furthermore, the results of animal experiments also demonstrated that intake too much fructose could prominently increase tumor volume, and silencing GLUT5 could significantly inhibit tumor proliferation. Conclusion: In conclusion, we demonstrate that ovarian cancer cells could utilize fructose for their growth, and restricting the fructose intake or targeting GLUT5 may be efficacious strategies for ovarian cancer therapy.

Keywords: GLUT5; fructose; ovarian cancer.

Figure 1

Ovarian cancer cells could utilize fructose for their growth. (A) Many kinds of cancer cell lines could utilize fructose. (B) Ovarian cancer cells grew at equivalent rates in 25 mM fructose medium and 25 mM glucose medium detected by MTT. (C) There was a concentration dependence in fructose utilization for cell growth. (D, E) The colony formation of ovarian cancer cells in 25 mM fructose medium and 25 mM glucose medium. (F) The migration of ovarian cancer cells in 25 mM fructose medium and 25 mM glucose medium. (G) The tumor grew in vivo after feeding fructose 30 days (*P<0.05, **P<0.01).

Figure 2

The affects of shGLUT5 in ovarian cancer cells. (A) The expression level of GLUT5 in ovarian cancer cells. (B) shRNA was used to knockdown GLUT5 in ovarian cancer cells. (C) The affect of shGLUT5 in OVCAR8 proliferation in 25 mM fructose medium and 25 mM glucose medium. (D) The affect of shGLUT5 in SKOV3 proliferation. (E, F) The affect of shGLUT5 in two-dimensional colony formation in 25 mM fructose medium. (G, H) The affect of shGLUT5 in 3D colony formation in 25 mM fructose medium detected by soft agar. (I, J) The affect of shGLUT5 in cell migration in 25 mM fructose medium. (**P<0.01).

Figure 3

The affects of sgGLUT5 in ovarian cancer cell line OVACR. (A) sgRNA was used to knockout GLUT5 in ovarian cancer cells. (B) The affect of sgGLUT5 in cell proliferation. (C) The affect of sgGLUT5 in two-dimensional colony formation. (D) Resuming GLUT5 in sgGLUT5 cells. (E) The proliferation rates of cells sgctrl, sgGLUT5, and sgGLUT5-GLUT5. (F) The colony formation of cells sgctrl, sgGLUT5, and sgGLUT5-GLUT5. (G) The migration ability of cells sgctrl, sgGLUT5, and sgGLUT5-GLUT5. (H) The cells of sgctrl, sgGLUT5, and sgGLUT5-GLUT5 growth for 30 days in vivo (**P<0.01).

Figure 4

The expression of GLUT5 in ovarian cancer. (A) The expression level of GLUT5 mRNA in ovarian cancer tissues and normal ovary tissues in the TCGA database. (B) The effect of GLUT5 mRNA on the free progress survival and overall survival of glioma patients in the TCGA database. (C) The expression level of GLUT5 in ovarian cancer tissues and normal ovary tissues detected by IHC. (D) The expression level of GLUT5 in different types of ovarian cancer. (E) The expression level of GLUT5 in different grades of ovarian cancer. (F) The expression level of GLUT5 in metastasis ovarian cancer and no-metastasis. (G) The expression level of GLUT5 in different clinical stages of ovarian cancer. (H) The effect of GLUT5 on the overall survival of ovarian cancer patients. (I) The effect of GLUT5 on 3-year survival of ovarian cancer patients.