22‐Oxa‐1,25‐dihydroxyvitamin D3 efficiently inhibits tumor growth in inoculated mice and primary histoculutre of cholangiocarcinoma

摘要: BACKGROUND: It is well known that 1α,25-Dihydroxyvitamin D3(1,25[OH]2D3) restrains cell proliferation and induces differentiation apoptosis in normal tumor cells. The authors of this report recently demonstrated 1,25(OH)2D3 effectively inhibits the cholangiocarcinoma (CCA) lines. antitumor activity underlying mechanism 22-oxa-D3, an analog vitamin D, mice tissue cultures from patients with CCA were further explored current study. METHODS: Cell growth cycle distribution examined cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay flow cytometry. Mice injected subcutaneously 4 × 106 at both flank sides intraperitoneal injections phosphate-buffered saline or 22-oxa-D3(15 μg/kg/day) for 17 days thereafter. Tumors removed next day. expression levels cyclin D1 cyclin-dependent kinase inhibitor p21 determined Western blot analysis immunohistochemistry. Growth inhibition 22-oxa-D3 fresh samples was analyzed using a histodrug response assay. RESULTS: 22-Oxa-D3 suppressed lines time-dependent dose-dependent manner. 22-Oxa-D3 arrested G1 phase to S suppression up-regulation p21. Supplementation CCA-inoculated significantly inhibited without hypercalcemia serious side effects. treatment also induced cellular CCA. CONCLUSIONS: 22-Oxa-D3 CCA. data encourage investigation its analogues as therapeutic agents Cancer 2010. © 2010 American Society.