The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer.

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer.
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塞来昔布对卵巢癌细胞和浆液性卵巢癌基因工程小鼠模型肿瘤生长的影响。

DOI:
10.18632/oncotarget.8659
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发表时间:
2016-06-28
期刊:
影响因子:
--
通讯作者:
Bae-Jump VL
Bae-Jump VL
中科院分区:
其他
文献类型:
--
作者:
Suri A;Sheng X;Schuler KM;Zhong Y;Han X;Jones HM;Gehrig PA;Zhou C;Bae-Jump VL

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我们的目的是评估 COX-2 抑制剂塞来昔布对 (1) 人卵巢癌细胞系和卵巢癌细胞原代培养物的增殖和凋亡的影响,以及 (2) 在肥胖和非肥胖条件下对浆液性卵巢癌基因工程小鼠模型中肿瘤生长的抑制作用。接触塞来昔布 72 小时后,可抑制三种卵巢癌细胞系和五种人类卵巢癌原代培养物中的细胞增殖。塞来昔布治疗导致所有卵巢癌细胞系中 G1 细胞周期停滞、诱导细胞凋亡、抑制细胞粘附和侵袭以及 hTERT mRNA 和 COX-2 蛋白表达减少。在喂食高脂肪饮食(肥胖)并接受塞来昔布治疗的 KpB 小鼠中,与对照动物相比,肿瘤重量减少了 66%。在喂食低脂饮食(非肥胖)的 KpB 小鼠中,塞来昔布治疗后肿瘤重量减少了 46%。通过免疫组织化学评估,在肥胖和非肥胖 KpB 小鼠的卵巢肿瘤中,与对照相比,塞来昔布治疗导致增殖减少、细胞凋亡增加以及 COX-2 和 MMP9 蛋白表达减少。在肥胖和非肥胖条件下,塞来昔布可显着降低 KpB 卵巢癌小鼠模型的血清 VEGF 水平和肿瘤中的血管密度。这项工作表明塞来昔布可能是一种用于预防和治疗卵巢癌的新型化疗药物,并且对肥胖和非肥胖女性都有潜在益处。
Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women.
DOI: 10.1002/cncr.24086
发表时间: 2009-02-15
期刊: CANCER
影响因子: 6.2
作者:
Leitzmann, Michael F.;Koebnick, Corinna;Danforth, Kim N.;Brinton, Louise A.;Moore, Steven C.;Hollenbeck, Albert R.;Schatzkin, Arthur;Lacey, James V., Jr.
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