Presentation Authors: Lin Yang*, Jun Yan, Hongqian Guo, Nanjing, China, People's Republic of
Introduction: Hypercholesterolemia was reported to be associated with several cancers, such as prostate cancer, breast cancer and colorectal cancer. Urinary bladder cancer (UBC) is one of the most common urogenital malignancies. Whether hypercholesterolemia plays a role in UBC progression remains unclear. Our objective was to investigate the influence of hypercholesterolemia on UBC progression by several mice models.
Methods: 1) Diet induced hypercholesterolemia model. Nude mice were fed with low fat no cholesterol diet (LFNC) or high fat high cholesterol diet (HFHC) w/o ezetimibe (EZ), which inhibited the absorption of cholesterol. T24 xenografts were injected once model established. Tumor growth, etc were measured. 2) BBN induced in situ bladder cancer model in wildtype mice and LDLR-/- mice. Tumor progression was analyzed. 3) MB49 allografts and tail vessel injected lung metastasis model. Allografts' growth and lung metastases were measured.
Results: 1. Diet induced hypercholesterolemia promoted UBC progression. (Figure 1) 2. BBN induced UBC was promoted in LDLR-/- mice, a spontaneous hypercholesterolemia mouse model. UBC in situ progressed much faster in LDLR-/- mice (Figure 2B) with more lymph node and lung metastases (Figure 2C and 2D). Shorter survival curve was found in LDLR-/- mice (Figure 2E). 3. Enhanced progression, metastasis of MB49 injected were found in LDLR-/- mice compared to those in wildtype mice. MB49 allografts' growth was enhanced in LDLR-/- mice with lung metastases which were not detected in wildtype mice (Figure 3A to 3C). Tail vessel injection induced lung metastasis of MB49 showed that enhanced metastasis ability was detected in LDLR-/- mice (Figure 3D to 3F).
Conclusions: Hypercholesterolemia could promote the progression of UBC, which was confirmed in several mice models.
Source of Funding: the National Natural Science Foundation of China (81372168, 81470116, 81672873 and 81572519)