Effect of Lycopene on Oral Squamous Cell Carcinoma Cell Growth by Inhibiting IGF1 Pathway

Abstract

Purpose

Lycopene has produced robust clinical effects and shows a promising chemopreventive in the oral cancer and precancerous lesions. However, much is still unknown about its mechanisms of the carotenoid in protecting against oral squamous cell carcinoma (OSCC). Insulin-like growth factor 1 (IGF1) pathway serves as a key regulatory signal pathway in the tumor microenvironment, which may be associated with the angiogenesis, tumorigenicity, and cancer proliferation. The current study was focused on elucidating the potential pathway played for lycopene to exert its function in treating with OSCC.

Materials and Methods

Firstly, we explored the dose- and time-response of CAL-27 and WSU-HN6 cells to lycopene. Both cells were incubated with various concentrations of lycopene (0.25, 0.5, 1, 2 µM). The inhibiting rate of cell proliferation was assessed using MTT assay. To observe the regulating effect of lycopene on OSCC, cell migration, apoptosis and tumor formation were detected in vitro and in vivo. The potential signaling pathways of OSCC cells treated with lycopene were analyzed by Affymetrix microarrays. And then, we investigated the changing of IGF1 signaling pathway, on the protein levels of tumor tissue after lycopene.

Results

Cell proliferation was inhibited by lycopene in a dose- and time-dependent manner. The optimum inhibition efficiencies for OSCC cells were also found. Further, the results also demonstrated that pre-treatment of OSCC with lycopene drastically induced cell apoptosis suppresses cell migration and tumor growth. Mechanistically, ingenuity pathway analysis further revealed that IGF1 pathway participate in killing effects on OSCC after treatment of lycopene. Lycopene may inhibit the pathway by regulating protein expression of IGF1, IGF binding protein (BP) 1, IGFBP3, transcription factor Jun/AP-1 (JUN), and forkhead box O1 (FOXO1).

Conclusion

These observations indicate that lycopene regulates OSCC cell growth by inhibiting IGF1 pathway, which may be a promising agent for the treatment of OSCC.

Keywords:

• lycopene
• insulin-like growth factor 1
• oral squamous cell carcinoma
• cell proliferation

Statement of Ethics

The study was approved by the Institutional Animal Care and Use Committee of the Peking University Health Science Center.

Disclosure

The authors declare that they have no financial or nonfinancial conflicts of interest for this work.