摘要
目的观察百里醌对胰腺癌裸鼠原位移植瘤生长和转移的影响及其作用机制。方法建立外科胰腺癌原位移植模型，随机分为4组：对照（Contr01）组、低剂量百里醌（L-TQ）组、高剂量百里醌（H—TQ）组和吉西他滨（GEM）组，第3周开始分别给予溶媒（1％乙醇）0．2ml／只、百里醌5mg／kg、百里醌20mg／kg和吉西他滨100mg／kg治疗。术后第8周处死裸鼠，测量胰腺肿瘤瘤重并计算抑瘤率；观察裸鼠肿瘤转移情况；免疫组织化学法检测肿瘤组织中细胞增殖因子（Ki-67）、X连锁凋亡抑制蛋白（XIAP）和基质金属蛋白酶（MMP）-9的表达。结果L-TQ组、H-TQ组和GEM组的抑瘤率分别为42．57％、64．11％和54．77％；与对照组相比，GEM组肿瘤转移未被明显抑制，而L-TQ组和H—TQ组肿瘤转移明显被抑制；与对照组相比较，L-TQ组和H-TQ组中Ki-67、XIAP和MMP-9的表达强度明显减弱，而GEM组中仅Ki-67表达下调。结论百里醌具有抑制胰腺癌裸鼠原位移植瘤生长和转移的作用，此作用机制可能与抑制XIAP和MMP-9的表达有关。
Objective To explore the anti-neoplastic and anti-metastatic effects of thymoquinone on the model of human pancreatic carcinoma established by surgical orthotopic implantation （SOI ） in nude mice. Methods After a 3-week implantation, 40 mice were randomized into 4 groups： control group, feed with 1% ethanol; low-dose thymoquinone group （L-TQ 5 mg/kg BW daily by i.g. ）, high-dose thymoquinone group （ H-TQ 20 mg/kg BW daily by i. g. ） and gemcitabine group （ GEM 100 mg/kg BW twice a week by i.p. ） （n = 10 each） . All treatment sessions lasted for 2 weeks. At Week 8 post-implantation, tumor weight, inhibition rate and the presence of metastasis were evaluated respectively after sacrificing. Immunohistochemistry was used to detect the positive expressions of Ki-67, XIAP （X-linked inhibitor of apoptosis protein） and MMP-9 （matrix metalloproteinase 9） in tumors. Results The tumor growth-inhibiting rates of L-TQ group, H-TQ group and GEM group were 42. 57% , 64. 11% and 54. 77% respectively. The rates of metastasis in L-TQ group and H-TQ group were 60% and 50% versus GEM group （ 100% ）. And the differences had statistical significance （ P 〈 0. 05 ）. The positive rates of Ki-67in group L-TQ and group H-TQ were 37% ＋3% and 32% ＋2% versus group GEM （55% -＋4% ）. And the differences had statistical significance （P 〈 0.05 ）. The positive rates of XIAP in group L-TQ and group H-TQwere 30%±3% and 28%±5% versus group GEM （56%±4% ）. And the differences had statistical significance （ P 〈 0. 05 ）. The positive rates of MMP-9 in group L-TQ and group H-TQ were 57%±7% and 53%±2% versus group GEM （73%±4%） . And the differences had statistical significance （P 〈 0. 05）. Conclusion Thymoquinone has the anti-neoplastic and anti-metastatic effects on the human pancreatic carcinoma in nude mice. And the above effects may be correlated with the down- regulated expressions of XIAP and MMP-9.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2011年第44期3111-3114,共4页
National Medical Journal of China
关键词
胰腺肿瘤
百里醌
转移
XIAP
MMP-9
Pancreatic neoplasms
Thymoquinone
Metastasis
X-linked inhibitor of apoptosis protein
Matrix metalloproteinase 9
