d-柠檬烯对裸鼠移植人胃癌生长和转移的抑制作用
Inhibition of growth and metastasis of human gastric cancer implanted in nude mice by d-limonene.
作者信息
Lu Xiao-Guang, Zhan Li-Bin, Feng Bing-An, Qu Ming-Yang, Yu Li-Hua, Xie Ji-Hong
机构信息
Department of General Surgery, Fourth Hospital of Dalian Medical University, Dalian 116001, Liaoning Province, China.
出版信息
World J Gastroenterol. 2004 Jul 15;10(14):2140-4. doi: 10.3748/wjg.v10.i14.2140.
AIM
To investigate the effects and mechanism of d-limonene on the growth and metastasis of gastric cancer in vivo.
METHODS
Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. One percent d-limonene was orally administered at dose of 15 ml/kg every other day for seven weeks. Eight weeks after implantation, tumor weight, inhibition rate, apoptotic index (AI), microvessel density (MVD), vascular endothelial growth factor (VEGF), variation of ultrastructure, and the presence of metastasis were evaluated, respectively, after the mice were sacrificed.
RESULTS
The tumor weight was significantly reduced in 5-FU group (2.55+/-0.28 g), d-limonene group (1.49+/-0.09 g) and combined treatment group (1.48+/-0.21 g) compared with the control group(2.73+/-0.23 g, P<0.05). In 5-FU group, d-limonene group, combined treatment group, the inhibition rates were 2.60%,47.58% and 46.84% and 0, respectively; AI was (3.31+/-0.33)%, (8.26+/-1.21)%, (20.99+/-1.84)% and (19.34+/-2.19)%, respectively; MVD was (8.64+/-2.81), (16.77+/-1.39), (5.32+/-4.26) and (5.86+/-2.27), respectively; VEGF expression was (45.77+/-4.79), (41.34+/-5.41), (29.71+/-8.92) and (28.24+/-8.55), respectively. The incidences of peritoneal metastasis also decreased significantly in 5-FU group(77.8%), d-limonene group (20.0%) and combined group (22.2%) compared with control group (100%) versus 62.5%,30% and 22.2%) (P<0.05). Liver metastasis was also inhibited and the incidences decreased significantly in 5-FU group, d-limonene group and combined group than that in control group (87.5% vs 55.5%, 20.0% and 22.2% respectively)(P<0.05). The incidence of ascites in control group, 5-FU group, d-limonene group and combined group was 25.0%, 22.2%, 0, 0, respectively and 12.5%, 11.1% 0, 0, with respect to the metastasis rate to other organs.
CONCLUSION
d-limonene has antiangiogenic and proapoptotic effects on gastric cancer, thereby inhibits tumor growth and metastasis. Combination of d-limonene with cytotoxic agents may be more effective.
目的
研究d - 柠檬烯对胃癌体内生长和转移的影响及其机制。
方法
将组织学完整的人肿瘤组织原位植入裸鼠胃壁，建立模拟人胃癌的转移模型。每隔一天以15 ml/kg的剂量口服1%的d - 柠檬烯，持续7周。植入8周后，处死小鼠，分别评估肿瘤重量、抑制率、凋亡指数（AI）、微血管密度（MVD）、血管内皮生长因子（VEGF）、超微结构变化及转移情况。
结果
与对照组（2.73±0.23 g）相比，5 - 氟尿嘧啶（5 - FU）组（2.55±0.28 g）、d - 柠檬烯组（1.49±0.09 g）和联合治疗组（1.48±0.21 g）的肿瘤重量显著降低（P<0.05）。5 - FU组、d - 柠檬烯组、联合治疗组的抑制率分别为2.60%、47.58%和46.84%，对照组为0；AI分别为（3.31±0.33）%、（8.26±1.21）%、（20.99±1.84）%和（19.34±2.19）%；MVD分别为（8.64±2.81）、（16.77±1.39）、（5.32±4.26）和（5.86±2.27）；VEGF表达分别为（45.77±4.79）、（41.34±5.41）、（29.71±8.92）和（28.24±8.55）。与对照组（100%）相比，5 - FU组（77.8%）、d - 柠檬烯组（20.0%）和联合组（22.2%）的腹膜转移发生率也显著降低（与62.5%、30%和22.2%相比）（P<0.05）。肝转移也受到抑制，5 - FU组、d - 柠檬烯组和联合组的肝转移发生率显著低于对照组（分别为87.5%对55.5%、20.0%和22.2%）（P<0.05）。对照组、5 - FU组、d - 柠檬烯组和联合组的腹水发生率分别为25.0%、22.2%、0、0，相对于其他器官转移率分别为12.5%、11.1%、0、0。
结论
d - 柠檬烯对胃癌具有抗血管生成和促凋亡作用，从而抑制肿瘤生长和转移。d - 柠檬烯与细胞毒性药物联合使用可能更有效。
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