PERIOD1 (PER1) has anti-apoptotic effects, and PER3 has pro-apoptotic effects during cisplatin (CDDP) treatment in human gingival cancer CA9-22 cells

PERIOD1 (PER1) has anti-apoptotic effects, and PER3 has pro-apoptotic effects during cisplatin (CDDP) treatment in human gingival cancer CA9-22 cells
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DOI:
10.1016/j.ejca.2011.02.025
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发表时间:
2011-07-01
影响因子:
8.4
通讯作者:
Kijima, Hiroshi
Kijima, Hiroshi
中科院分区:
医学1区
文献类型:
--
作者:
Sato, Fuyuki;Wu, Yunyan;Kijima, Hiroshi

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PERIOD(PER)蛋白是转录调节因子,参与昼夜节律、睡眠稳态、细胞增殖和肿瘤进展。我们以前的研究表明,PER 1的表达与人胰腺癌和肝细胞癌细胞的凋亡调控有关。然而,PER在口腔癌中的意义尚未报道,并且抗肿瘤药物诱导牙龈癌细胞凋亡的详细分子机制还不清楚。我们研究PER 1和PER 3是否参与人牙龈癌CA 9 -22细胞凋亡的调节。PERI的表达。CA 9 -22细胞经顺铂(cisplatin:CDDP)处理后,PER 1和PER 3的表达分别上调和下调,而CDDP处理对PER 1的表达几乎没有影响。人牙龈成纤维细胞(HGF-1)中的PER 3。我们发现,短干扰RNA(siRNA)介导的PER 1敲低增强CA 9 -22细胞的凋亡,并且PER 1调节凋亡相关分子Bim的量。另一方面,PER 3敲低对CDDP诱导的CA 9 -22细胞凋亡具有抑制作用。这些结果表明,PERI表达的改变。PER 3与CA 9 -22细胞凋亡有关。免疫组化结果显示,PER 1在牙龈癌组织中呈强阳性表达,而PER 3在非癌组织中呈强阳性表达,提示PER 1在牙龈癌组织中表达较强。和PER 3分别对人牙龈癌CA 9 -22细胞具有抗凋亡和促凋亡作用。PERI的平衡。PER 3可能调节牙龈癌细胞的凋亡反应。(C)2011爱思唯尔有限公司保留所有权利。
PERIOD (PER) proteins are transcriptional regulators that are involved in circadian rhythms, sleep homeostasis, cell proliferation and tumour progression. We previously showed that the expression of PER1 was related to the regulation of apoptosis in human pancreatic cancer and hepatocellular carcinoma cells. However, the significance of PER in oral cancer has not been reported, and the detailed molecular mechanisms by which anti-tumour drug induces apoptosis in gingival cancer cells are not well understood. We examined whether PER1 and PER3 are involved in the regulation of apoptosis in human gingival cancer CA9-22 cells. The expression of PERI. and PER3 was upregulated and downregulated, respectively, by cis-diamminedichloroplatinum (II) (cisplatin: CDDP) treatment in CA9-22 cells, whereas CDDP treatment had little effects on the expression of PERI. and PER3 in human gingival fibroblasts (HGF-1). We found that short interference RNA (siRNA)-mediated knockdown of PER1 enhanced apoptosis of CA9-22 cells, and that PER1 regulated the amount of Bim, an apoptosis-related molecule. On the other hand, PER3 knockdown had an inhibitory effect on the apoptosis of CA9-22 cells induced by CDDP treatment.. These results suggest that the alternation of expression of PERI. and PER3 was related to the apoptosis of CA9-22 cells. Furthermore, PER1 was intensely stained in the gingival cancer tissues, whereas PER3 was significantly stained in the non-tumour tissues by immunohistochemistry.These findings suggest that PERI. and PER3 have anti-apoptotic and pro-apoptotic effects in human gingival cancer CA9-22 cells, respectively. The balance of PERI. and PER3 may modulate apoptotic reactions in gingival cancer cells. (C) 2011 Elsevier Ltd. All rights reserved.