苦参碱联合5-FU抑制人胃癌裸鼠移植瘤的生长作用及机制

【目的】研究苦参碱(matrine,Ma)与5-氟尿嘧啶(5-FU)联合应用对人胃腺癌SGC-7901裸鼠移植瘤的抑制作用及可能机制。【方法】将人胃腺癌SGC-7901细胞株接种于BALB／cA裸鼠皮下,形成移植瘤后传3代;取生长旺盛期的瘤组织约1．5 mm3,无菌接种于裸鼠右侧腋窝皮下,待肿瘤生长至100-300mm3后将动物随机分为6组,即模型组、5-FU组(50 mg/kg)、Ma低剂量组(50 mg/kg)、Ma高剂量组(100 mg/kg)、Ma低剂量 5-FU组、Ma高剂量 5-FU组;各组分别按设计剂量腹腔给药,35 d后测量各组裸鼠瘤径和肿瘤体积,计算相对肿瘤体积(VR)和相对肿瘤抑制率(pinhibitory);采用免疫组化法检测荷瘤组织中凋亡相关蛋白bcl-2、bax活性和caspase-3的表达情况。【结果】Ma高剂量 5-FU组抑瘤作用与模型组、 Ma高剂量组、5-FU组比较均显著增强(P<0．05或P<0．01),Ma低剂量 5-FU组抑瘤作用也见增强,但与其他组比较无显著性差异;各给药组均可不同程度下调bcl-2表达,上调bax表达,提高活性caspase-3表达,与模型组比较具有显著性差异(P<0．05或P<0．01);Ma高、低剂量分别与5-FU合用后,该调节作用较单独使用显著增强(P<0．05或P<0．01), 并呈现剂量依赖关系。【结论】苦参碱与5-FU联合应用具有一定的协同增效作用,其机制可能与调节凋亡相关蛋白的表达, 诱导胃癌细胞凋亡有关。

Inhibitory Effect of Matrine Combined with 5-fluorouracil on the Growth of Implanted Human Gastric Tumor in Nude Mice and Its Mechanism

[Objective] To investigate the inhibitory effect of matrine (Ma) combined with 5-fluorouracil (5-FU) on the growth of implanted human gastric tumor SGC-7901 in nude mice and to explore its mechanism. [Methods] SGC-7901 strain was implanted subcutaneously into BALB/cA nude mice to induce the implanted human gastric tumor. After subculture for three generations, the tumor tissues about 1.5 mm in size were inoculated in the subcutaneous part of right axillary fossa in nude mice. When the tumor grew to the size of 100 - 300 mm3, the mice were randomized into 6 groups: model, 5-FU (50 mg/kg), low-dose Ma (50 mg/kg), high-dose Ma (100 mg/kg), low-dose Ma 5-FU and high-dose Ma 5-FU. The mice were given the corresponding drugs according to the experimental design. After a 35-day treatment, the diameter and the size of the tumor were detected to measure the relative tumor volume (VR) and relative tumor inhibitory rate (p inhibitory),and the expression of apoptosis-associated protein of bcl-2, bax and active caspase-3 was examined by immunohistochemical method. [Results] The tumor-inhibitory effect in high-dose Ma 5-FU was stronger than that in the model group, high-dose Ma group and 5-FU group (P<0.05 or P<0.01); the effect in low-dose Ma 5-FU group was also increased, but the difference was insignificant as compared with the other groups. The expression of bcl-2 decreased, and the expression of bax and active caspase-3 increased in the treatment groups (P <0.05 or P < 0.01 compared with the model group) . The regulatory effect on protein expression was enhanced when Ma in high dose or in low dose was used with 5-FU ( P < 0.05 or P < 0.01), and the effect was in a dose-dependent manner. [Conclusion] Ma has a synergistic action with 5-FU on implanted human gastric tumor, and its mechanism may be related to the regulation of apoptosis-associated protein expression and induction of gastric tumor cell apoptosis.