Potentiating NK cell activity by combination of Rosuvastatin and Difluoromethylornithine for effective chemopreventive efficacy against Colon Cancer.
Potentiating NK cell activity by combination of Rosuvastatin and Difluoromethylornithine for effective chemopreventive efficacy against Colon Cancer.
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通过瑞士瓦伐他汀和差甲基氨基氨酸的结合来增强NK细胞活性，从而有效地对结肠癌的化学预防疗效。
DOI：
10.1038/srep37046
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发表时间：
2016-11-14
影响因子：
4.6
通讯作者：
Rao CV
中科院分区：
文献类型：
--
作者：
Janakiram NB;Mohammed A;Bryant T;Zhang Y;Brewer M;Duff A;Biddick L;Singh A;Lightfoot S;Steele VE;Rao CV
结直肠癌（CRC）是癌症相关死亡的第二大原因。一个成功的策略，以提高化学预防效果是通过下调肿瘤多胺和增强NK细胞活性。用氧化偶氮甲烷（AOM）诱发雄性F344大鼠结肠癌。AOM给药后8周，动物饲喂含瑞舒伐他汀和二氟甲基鸟氨酸（DFMO）单独和联合的饲料，持续40周。与未处理的大鼠相比，两种药物均显示出对腺癌多样性和发病率的显著抑制，且无毒性。与低剂量瑞舒伐他汀（29%）和DFMO（46%）相比，低剂量瑞舒伐他汀+DFMO可将结肠腺癌多重性抑制76%，表明具有相加疗效。此外，低剂量联合用药导致结肠腺癌进展延迟。与未处理的结肠肿瘤相比，DFMO、瑞舒伐他汀和/或组合显著降低多胺含量并增加表达穿孔素加IFN-γ的肿瘤内NK细胞。暴露于DFMO、瑞舒伐他汀或组合的脾NK细胞的进一步离体分析导致具有穿孔素表达的NK增加。这是关于瑞舒伐他汀单药或使用临床相关他汀类药物加DFMO剂量的联合策略的首次报告，显示出对结肠腺癌的显著抑制作用及其增加功能性NK细胞的潜力。这种策略有可能在结肠癌高危人群中进行进一步的测试。
Colorectal cancer (CRC) is the second highest cause of cancer-related deaths. A successful strategy to improve chemopreventive efficacies is by down-regulating tumor polyamines and enhancing NK cell activities. Colonic carcinogenesis was induced by azoxymethane (AOM) in male F344 rats. Eight weeks after AOM treatment, animals were fed diets containing Rosuvastatin and difluromethylornithine (DFMO) individually and in combination for 40 weeks. Both agents showed significant suppression of adenocarcinoma multiplicity and incidence with no toxicity compared to untreated rats. Low-dose Rosuvastatin plus DFMO suppressed colon adenocarcinoma multiplicity by 76% compared to low-dose Rosuvastatin (29%) and DFMO (46%), suggesting additive efficacy. Furthermore, low-dose combination caused a delay in colonic adenocarcinoma progression. DFMO, Rosuvastatin and/or combinations significantly decreased polyamine content and increased intra-tumoral NK cells expressing perforin plus IFN-γ compared to untreated colon tumors. Further ex-vivo analysis of splenic NK cells exposed to DFMO, Rosuvastatin or combination resulted in an increase of NKs with perforin expression. This is the first report on Rosuvastatin alone or combination strategy using clinically relevant statin plus DFMO doses which shows a significant suppression of colon adenocarcinomas, and their potential in increasing functional NK cells. This strategy has potential for further testing in high risk individuals for colon cancer.
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影响因子：
5
作者：
COOPER, KD;SHUKLA, JB;RENNERT, OM
通讯作者：
RENNERT, OM
影响因子：
3
作者：
Erbas, Hakan;Bal, Oguz;Cakir, Erol
通讯作者：
Cakir, Erol
影响因子：
3.2
作者：
BARDOCZ, S;GRANT, G;PUSZTAI, A
通讯作者：
PUSZTAI, A
影响因子：
8.8
作者：
Chamaillard, L;CatrosQuemener, V;Moulinoux, JP
通讯作者：
Moulinoux, JP
DOI：
10.1016/0020-711x(90)90262-2
发表时间：
1990-01-01
期刊：
INTERNATIONAL JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
COLOMBATTO, S;FASULO, L;GRILLO, MA
通讯作者：
GRILLO, MA