類胡蘿蔔素對人類口腔癌KB細胞PCNA和cyclin D1表現之影響

Effects of Carotenoids on PCNA and Cyclin D1 in Human Oral KB Cell

廖佳慧(Chia-Hui Liao)

指導教授 ： 黃士懿博士

臺北醫學大學/公共衛生暨營養學院/保健營養學研究所/碩士(2004年)

摘要

口腔癌高居台灣男性十大癌症死因之第四名，且發生率與死亡率逐年上升。細胞癌化過程中，增殖是必要的過程，而細胞的增殖由若干因子調控，如：cyclin D1和增殖細胞核抗原（proliferating cell nuclear antigen, PCNA）。研究指出，PCNA和cyclin D1會隨著口腔細胞癌化的進展而增加。類胡蘿蔔素為脂溶性維生素，可經由調控分子之作用機轉，進而抑制或預防癌症的發生。本實驗以0（0.1% THF）、5、10、20和30 μM類胡蘿蔔素（β-胡蘿蔔素、蕃茄紅素、木質黃素）培養KB cell 24小時，分析PCNA和cyclin D1之表現、觀察細胞週期之變化，探討不同類胡蘿蔔素抑制人類口腔癌細胞KB cell增殖的機制。結果顯示，類胡蘿蔔素皆可顯著抑制KB cell生長（p < 0.05），且抑制能力為木質黃素最佳，蕃茄紅素次之，最後為β-胡蘿蔔素。類胡蘿蔔素亦都降低cyclin D1和PCNA的表現。10 μM β-胡蘿蔔素即可抑制PCNA表現，而10 μM木質黃素即可抑制cyclin D1表現，且使細胞停滯在G0/G1期，也減少了S期之細胞數目；蕃茄紅素則使G0/G1期細胞數目減少，G2/M期之細胞數目增加。顯示類胡蘿蔔素抑制口腔癌細胞增殖，藉由在不同細胞週期的調控，皆可抑制人類口腔癌細胞KB cell的增殖。

關鍵字

口腔癌 ； 增殖細胞核抗原 ； Cyclin D1 ； 類胡蘿蔔素

並列摘要

Oral cancer was the fourth leading cause of cancer deaths among men in Taiwan. Cyclin D1 was an important nuclear protein in G1/S phase of cell cycle. Proliferating cell nuclear antigen (PCNA) served as a co-factor for DNA polymerase δ in S phase and played a critical role in DNA synthesis and cell proliferation. In previous studies, PCNA and cyclin D1 expression were increased with the progression of oral carcinogensis. Carotenoids were common lipotrophic phytochemicals in nature which prevent cancers by interfering protein expression in cell cycle. Thus the present study was to evaluate the mechanism of carotenoids (β-carotene, lycopene and lutein) on inhibition of human oral epidermoid carcinoma cell line (KB cell) proliferation. Cyclin D1 and PCNA were evaluated as biomarkers of cell differntation. In result, all carotenoids exerted a significant inhibitory effect on KB cell proliferation, and showed the inhibitory ptoency in order of was lutein > lycopene > β-carotene on downregulated of cyclin D1 and PCNA expression. In lower concentration (10 μM), β-carotene and lutein inhibited PCNA and cyclin D1 expression, respectively, following arrest in G0/G1 phase and reduced cell number in S phase, however, lycopene reduced cell number in G0/G1 phase and arrest in G2/M phase. The study suggests carotenoids inhibit oral KB cell proliferation by modulating different protein expression of cell cycle.

並列關鍵字

oral cancer ； PCNA ； Cyclin D1 ； carotenoids

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