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高剂量维生素 C 给药抑制小鼠卵巢中黑色素瘤细胞的侵袭和增殖。

High-Dose Vitamin C Administration Inhibits the Invasion and Proliferation of Melanoma Cells in Mice Ovary.

机构信息

Department of Pharmaceutical Science, Suzuka University of Medical Science.

Medical Nakanishi Co., Ltd.

出版信息

Biol Pharm Bull. 2021;44(1):75-81. doi: 10.1248/bpb.b20-00637.

Abstract

Several studies have been conducted to explore the anticancer effects of vitamin C (VC). However, the effect of high-dose VC administration on melanoma is still unknown. Therefore, in this study, we investigated the effects of high-dose VC (4 g/kg) on the invasion and proliferation of melanoma cells in various organs of mice. B16 melanoma cells (1 × 10 cells/100 µL) were intravenously injected into the tails of female mice, and VC solution (4 g/kg) was orally administered once a day for 14 d. On the 15th day, samples from the liver, lungs, jejunum, and ovaries were collected and analyzed for invasion and proliferation of melanoma cells. Oral VC administration decreased the number of dihydroxyphenylalanine (DOPA)-positive cells and gp100-positive melanoma cells in the ovaries and suppressed the invasion and proliferation of melanoma. Compared to melanoma-administered mice, macrophage inflammatory protein-2 levels and number of neutrophils were increased in the VC + melanoma-administered mice. Furthermore, the concentrations of VC, iron, and hydrogen peroxide, and the number of terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive cells were significantly increased in the ovaries of VC + melanoma-administered mice compared to those of melanoma-administered mice. These results suggest that VC can reduce the invasion and proliferation of melanoma cells in the ovaries, and neutrophils in the ovaries play an important role in achieving this melanoma-suppressive effect.

摘要

已有多项研究探索了维生素 C(VC)的抗癌作用。然而,高剂量 VC 给药对黑色素瘤的影响尚不清楚。因此,在本研究中,我们研究了高剂量 VC(4g/kg)对小鼠各器官中黑色素瘤细胞侵袭和增殖的影响。将 B16 黑色素瘤细胞(1×10 个细胞/100μL)尾静脉注入雌性小鼠体内,每天口服 VC 溶液(4g/kg)一次,连续 14d。第 15 天,收集肝脏、肺、空肠和卵巢样本,分析黑色素瘤细胞的侵袭和增殖情况。口服 VC 给药减少了卵巢中 DOPA 阳性细胞和 gp100 阳性黑色素瘤细胞的数量,并抑制了黑色素瘤的侵袭和增殖。与黑色素瘤给药组相比,VC+黑色素瘤给药组小鼠的巨噬细胞炎症蛋白-2 水平和中性粒细胞数量增加。此外,与黑色素瘤给药组相比,VC+黑色素瘤给药组小鼠卵巢中 VC、铁和过氧化氢的浓度以及末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记(TUNEL)阳性细胞的数量显著增加。这些结果表明,VC 可减少卵巢中黑色素瘤细胞的侵袭和增殖,卵巢中的中性粒细胞在发挥这种抑制黑色素瘤的作用中起重要作用。

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