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19-去甲-1α-25-二羟维生素 D2 对胃癌细胞及腹膜转移模型的抑制作用。

Suppressive effect of 19-nor-1α-25-dihydroxyvitamin D2 on gastric cancer cells and peritoneal metastasis model.

机构信息

Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, Korea.

出版信息

J Korean Med Sci. 2012 Sep;27(9):1037-43. doi: 10.3346/jkms.2012.27.9.1037. Epub 2012 Aug 22.

Abstract

The active metabolite of vitamin D, 1,25-dihydroxyvitamin D(3) (calcitriol), inhibits the growth of several types of human cancer cells in vitro, but its therapeutic use is limited because it causes hypercalcemia. Among its analogs, 19-nor-1,25-dihydroxyvitamin D(2) (paricalcitol), has fewer calcemic effects and exhibits an activity equipotent to that of calcitriol. We assessed the antitumor and anti-inflammatory effects of paricalcitol in gastric cancer cells, and evaluated the potential role of vitamin D in the treatment of peritoneal metastatic gastric cancer. In this study, treatment with paricalcitol inhibited gastric cancer cell growth and induced cell cycle arrest. Paricalcitol also induced apoptosis and showed anti-inflammatory activity. Moreover, the growth of intraperitoneal metastases in vivo was reduced in mice treated with paricalcitol. (18)F-FDG uptake was significantly lower in the paricalcitol group compared to control group (SUV; control group 13.2 ± 5.3 vs paricalcitol group 4.5 ± 3.0). Intraperitoneal tumor volume was significantly lower in paricalcitol treated mice (control group 353.2 ± 22.9 mm(3) vs paricalcitol group 252.0 ± 8.4 mm(3)). These results suggest that the vitamin D analog, paricalcitol, has anticancer activity on gastric cancer cells by regulation of the cell cycle, apoptosis, and inflammation.

摘要

维生素 D 的活性代谢物 1,25-二羟维生素 D(3)(骨化三醇),可抑制多种类型的人类癌细胞在体外生长,但由于其会引起高钙血症,其治疗用途受到限制。在其类似物中,19-去甲-1,25-二羟维生素 D(2)(帕立骨化醇),钙作用较小,且与骨化三醇的活性相当。我们评估了帕立骨化醇对胃癌细胞的抗肿瘤和抗炎作用,并评估了维生素 D 在治疗腹膜转移性胃癌中的潜在作用。在这项研究中,帕立骨化醇治疗抑制了胃癌细胞生长并诱导细胞周期停滞。帕立骨化醇还诱导细胞凋亡并表现出抗炎活性。此外,帕立骨化醇治疗组小鼠体内腹膜转移的生长减少。与对照组相比,帕立骨化醇组的 18F-FDG 摄取显著降低(SUV;对照组 13.2±5.3 比帕立骨化醇组 4.5±3.0)。帕立骨化醇治疗组小鼠的腹腔肿瘤体积明显小于对照组(对照组 353.2±22.9 mm3 比帕立骨化醇组 252.0±8.4 mm3)。这些结果表明,维生素 D 类似物帕立骨化醇通过调节细胞周期、凋亡和炎症对胃癌细胞具有抗癌活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acdb/3429820/b99f49a9db34/jkms-27-1037-g001.jpg

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