(P31-045-23) The Differential Effects of Silibinin on Obesity-Associated Visfatin and Liver Cancer

Objectives: It has yet to be determined if inhibition of visfatin, a pro-inflammatory adipocytokine upregulated by obesity, is sufficient to prevent or delay the progression of liver cancer. The use of dietary compounds may break the pro-inflammatory cycle induced by the obese state such as silibinin, a polyphenol in milk thistle seed, which has been shown to have anti-inflammatory and anti-tumorigenic properties. Studies have yet to determine whether silibinin can be used to break the obesity-cancer link to delay progression of liver cancer by inhibiting visfatin signaling. The objective of this cell culture and mouse study is to determine the efficacy of silibinin in the prevention of obesity-associated liver cancer progression.

Methods: SNU-449 and HepG2 liver cancer cells were exposed to either control, visfatin (80 ng/ml), visfatin + silibinin (40 μM), silibinin. Proliferation, lipogenesis, lactate dehydrogenase secretion, and ROS production were measured. Immunoblot was used to measure phospho-Akt, phospho-Erk, NF-kB, and actin. Eight-week-old C57BL/6J male mice were randomized to a high-fat DIO (n=20) or control diet (n=20). At 14 weeks, mice were injected subcutaneously with syngeneic Hepa1-6 liver cancer cells. At 15-weeks, half of the DIO and control mice received peritoneal injections of silibinin 3 times a week for 2 weeks. Tumors were measured and will be assessed for visfatin, Akt, Erk, and NF-kB protein expression. Tumor analysis is on-going and will be presented at time of the conference.

Results: SNU-449 and HepG2 cells exposed to visfatin significantly increased cell proliferation and lipogenesis when compared to control, and the addition of silibinin inhibited the visfatin-induced proliferation and lipogenesis in both cell lines. Visfatin increased the phosphorylation of Akt and Erk, and NF-kB expression, and silibinin differently suppressed phosphorylation of Akt and Erk in liver cancer cells. DIO tumors were 72% larger compared to control (P >0.05). Silibinin decreased tumor growth by 34% compared to DIO tumors without silibinin.

Conclusions: Silibinin differentially inhibits visfatin-induced cell growth, lipogenesis, and promotes cytotoxicity in liver cancer cells. Further research is warranted to determine if silibinin inhibits obesity-associated liver cancer development.

Funding Sources: Texas State University Funding