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精胺酸添加對異種移植裸鼠大腸癌細胞生長之影響

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精胺酸添加對異種移植裸鼠大腸癌細胞生長之影響

胡雅梅 李正中 蔡佑靈 葉松鈴 台北醫學大學保健營養學系

摘要 :

本研究探討精胺酸 (Arginine, Arg) 添加對異種 移植裸鼠大腸癌細胞生長之影響。實驗培養人類大腸 直腸腺癌細胞株 SW-480 ,以 25 號針頭注射針注入 1 00μl 細胞液 (1*106 個細胞 ) 於裸鼠背部右側皮下後隨 機分成兩組,控制組 (Control 組 ) 給予不含 Arg 之粉 狀飼料,實驗組 (Arg 組 ) 給予富含 Arg 的粉狀飼料,

兩組飼料以等氮量、等熱量配製。經五週餵食後將裸 鼠犧牲,取腫瘤細胞及脾臟分析。結果顯示在實驗後

Arg 組腫瘤體積顯著小於 Control 組;在腫瘤均質液 Arg 組一氧化氮 (nitric oxide, NO) 的濃度顯著高於 Control 組,而促血管新生因子中 Arg 組血管內皮生長 因子受器 (vascular endothelial growth factor receptor, VEGF-R) 、基質金屬蛋白酶 (matrix metalloproteina e, MMP)-2 、

MMP-9 皆顯著低於 Control 組,此外 Arg 組胰臟內自 然殺手細胞 (natural killer cell, NK) 活性顯著高於 Co ntrol 組。故推測飲食中添加 Arg 可增加一氧化氮在體 內的表現量及自然殺手細胞活性,並減少促血管新生 因子的生成,而

材料與方法 :

. 實驗設計 :

將人類大腸直腸腺癌細胞株 SW-480 以 25 號 針頭注射針注入 100μl 細胞液 (1*106 個細胞 ) 於裸鼠 背部右側皮下後,隨機分成兩組, Control 組給予不含 Arg 之粉狀飼料, Arg 組給予富含 Arg 的粉狀飼料,兩 組飼料以等

. 分析項目 :

定期測量體重及腫瘤體積。犧牲後取腫瘤組織 分析 NO 濃度和促血管新生因子中血管內皮生長因子中 VEGF 及 VEGF-R 和 MMP-2 、 MMP-9 之表現量 。

取脾臟測

. 統計方法 :

數據以 means ± SEM 表示,進行 Student‘s t-test ,

結果 :

NK cell 活性。

Fig. 1. Average body weights and tumor volume of cont rol and Arg groups.; *Significantly different from the

p < 0.05 表示有統計上的差異。

Post tumor inoculation day

0 10 20 30 40

Body Weight ( g )

0 5 10 15 20 25 30 35 40

Control Arg diet

post tumor inoculation day

0 10 20 30 40

Tumor volumn (mm

3 )

0 200 400 600 800 1000 1200 1400

Control Arg diet

結論 :

給予富含 Arg 飲食的裸鼠其直腸腫瘤細胞體積顯 著低於給予一般粉狀飼料的裸鼠。其原因為 Arg 可增加 N O 在體內的表現量和自然殺手細胞活性,並減少促血管新 生因子中 VEGF-R 及 MMP-2 、 MMP-9 的生成,進而抑 制腫瘤的細胞生長。

抑制腫瘤細胞生長。

氮量、等熱量配製,餵食五週後犧牲。

VEGF

Arg Con

VEGF ( pg / g protein )

0 2 4 6 8 10 12

14 Arg Diet

Control

VEGF-R

VEGF-R ( pg / g protein )

0 200 400 600 800

MMP-2 (ng/mL)

0 100 200 300 400

MMP-9 (ng/mL)

0 1 2 3 4 5 6 7 Arg Diet

Control

MMP-2 MMP-9

NK cell activity (%)

0 5 10 15 20 25

Arg Diet Control

Fig. 2. Concentration of nitric oxide (NO) in tumor

homogenate.* Significantly different from the control group.

control group.

NO

( mM / g protein )

0 2 4 6 8 10 12 14 16

Arg Diet Control

Fig. 3. Concentrations of A) VEGF and VEGF-R, B) MMP-2 and MMP-9 in tumor homogenates.

A B

* Significantly different from the control group.

Fig. 4. Activity of natural killer (NK) cell in spleen.; * Significantly different from the control group.

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