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類胡蘿蔔素對人類口腔癌 KB 細胞 PCNA 和 cyclin D1 表現之影響

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類胡蘿蔔素對人類口腔癌 KB 細胞 PCNA 和 cyclin D1 表現之影響

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 a ntigen, 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。

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

Oral cancer was the fourth leading cause of cancer deaths among men in Taiwan. C yclin 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 phas e and played a critical role in DNA synthesis and cell proliferation. In previous stud ies, PCNA and cyclin D1 expression were increased with the progression of oral ca rcinogensis. Carotenoids were common lipotrophic phytochemicals in nature which prevent cancers by interfering protein expression in cell cycle. Thus the present stu dy 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 s

howed the inhibitory ptoency in order of was lutein > lycopene > β-carotene on do

wnregulated of cyclin D1 and PCNA expression. In lower concentration (10 μM),

β-carotene and lutein inhibited PCNA and cyclin D1 expression, respectively, follo

wing 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 expres

sion of cell cycle.

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