Calcitriol, the active metabolite of vitamin D, has been widely studied for its preventive and therapeutic activity against several cancers including oral squamous cell carcinoma (OSCC). However, the impact of dietary vitamin D supplementation on initiation and progression of OSCC is unclear. To address this gap in knowledge, we conducted preclinical trials using the 4-nitroquinoline-1-oxide 4NQO carcinogen model of oral carcinogenesis. Female C57BL/6 mice were maintained on one of three vitamin D diets [25 IU, 100 IU, 10,000 IU] and exposed to 4NQO in drinking water for 16 weeks followed by regular water for 10 weeks. Body weight measurements obtained through the study duration did not reveal any differences between the three diets. Animals on 100 IU diet showed lower incidence of high-grade dysplasia/OSCC and higher CD3 + T cells compared to animals on 25 IU and 10,000 IU diets. Serum 25OHD3 levels were highest in animals on 10,000 IU diet at week 0 prior to carcinogen exposure but showed ∼50 % reduction at week 26. Histologic evaluation revealed highest incidence of OSCC in animals maintained on 10,000 IU diet. Animals on 100 IU and 10,000 IU diets showed higher vitamin D receptor VDR and CYP24A1 immunostaining in high-grade dysplastic lesions and OSCC compared to normal tongue. Validation studies performed in a 4NQO-derived OSCC model showed that short-term treatment of animals on a 25 IU diet with calcitriol significantly inhibited tumor growth compared to controls but did not affect tumor growth in animals on reference diet 1000 IU. Collectively, our results highlight the complex dynamics between vitamin D status and oral carcinogenesis. Our observations also suggest that therapeutic benefits of short-term calcitriol treatment may be more pronounced in vitamin D deficient hosts.

中文翻译：

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饮食中维生素D对口腔癌的发生和发展的影响。

钙三醇是维生素D的活性代谢产物，由于其对多种癌症（包括口腔鳞状细胞癌（OSCC））的预防和治疗活性，已经得到了广泛的研究。但是，饮食中维生素D对OSCC起始和进展的影响尚不清楚。为了解决这一知识空白，我们使用口腔癌发生的4-硝基喹啉-1-氧化物4NQO致癌物模型进行了临床前试验。雌性C57BL / 6小鼠维持三种维生素D饮食中的一种[25 IU，100 IU，10,000 IU]，并在饮用水中暴露于4NQO达16周，然后定期饮水10周。在研究期间获得的体重测量结果未显示三种饮食之间的任何差异。与接受25 IU和10,000 IU饮食的动物相比，接受100 IU饮食的动物表现出高度不典型增生/ OSCC的发生率较低，而CD3 + T细胞却较高。暴露于致癌物前第0周，在10,000 IU饮食中的动物血清25OHD3水平最高，但在第26周时显示降低约50％。组织学评估显示，在10,000 IU饮食中维持动物的OSCC发生率最高。与正常舌头相比，在100 IU和10,000 IU饮食下的动物在严重增生性病变和OSCC中表现出更高的维生素D受体VDR和CYP24A1免疫染色。在源自4NQO的OSCC模型中进行的验证研究表明，与对照相比，使用钙三醇对25 IU饮食的动物进行短期治疗显着抑制了肿瘤的生长，但不影响参考饮食1000 IU的动物的肿瘤生长。总的来说，我们的研究结果突出了维生素D状态与口腔癌变之间的复杂动力学。我们的观察结果还表明，在缺乏维生素D的宿主中，短期骨化三醇治疗的治疗效果可能更明显。