Tao Anqi, Wang Xing, Li Cuiying
Central Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China.
Department of Stomatology, Chinese PLA General Hospital, Beijing 100853, People's Republic of China.
Cancer Manag Res. 2021 Jan 26;13:723-732. doi: 10.2147/CMAR.S283927. eCollection 2021.
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.
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.
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).
These observations indicate that lycopene regulates OSCC cell growth by inhibiting IGF1 pathway, which may be a promising agent for the treatment of OSCC.
番茄红素已产生显著的临床效果，并在口腔癌及癌前病变中显示出有前景的化学预防作用。然而，关于这种类胡萝卜素预防口腔鳞状细胞癌（OSCC）的机制仍有很多未知之处。胰岛素样生长因子1（IGF1）通路是肿瘤微环境中的关键调节信号通路，可能与血管生成、致瘤性和癌症增殖有关。当前研究聚焦于阐明番茄红素在治疗OSCC中发挥作用的潜在途径。
首先，我们探究了CAL-27和WSU-HN6细胞对番茄红素的剂量和时间反应。两种细胞均用不同浓度的番茄红素（0.25、0.5、1、2 μM）孵育。使用MTT法评估细胞增殖抑制率。为观察番茄红素对OSCC的调节作用，在体外和体内检测细胞迁移、凋亡和肿瘤形成。用Affymetrix微阵列分析经番茄红素处理的OSCC细胞的潜在信号通路。然后，我们研究了番茄红素处理后肿瘤组织蛋白水平上IGF1信号通路的变化。
番茄红素以剂量和时间依赖性方式抑制细胞增殖。还发现了对OSCC细胞的最佳抑制效率。此外，结果还表明，用番茄红素预处理OSCC可显著诱导细胞凋亡、抑制细胞迁移和肿瘤生长。从机制上讲， Ingenuity通路分析进一步揭示，IGF1通路参与了番茄红素处理后对OSCC的杀伤作用。番茄红素可能通过调节IGF1、IGF结合蛋白（BP）1、IGFBP3、转录因子Jun/AP-1（JUN）和叉头框O1（FOXO1）的蛋白表达来抑制该通路。
这些观察结果表明，番茄红素通过抑制IGF1通路调节OSCC细胞生长，这可能是一种有前景的OSCC治疗药物。
