Page 24 - 《中国药房》2021年第1期

were inoculated with hepatoma cells H22 in the left armpit to establish tumor bearing models. After 24 h of inoculation，normal
group and model group were intragastrically given normal saline， and administration groups were intragastrically given
corresponding drugs，once a day，for 10 days. On the second day after the last administration，the general conditions of mice in
each group were observed；the body mass，thymus index（LI），spleen index（SI）were measured；the tumor inhibition rate was
detected. The effect（q）of combination therapy was evaluated by King’s formula. The counts of WBC，RBC and PLT，serum
contents of ALT，ALT，Scr and BUN were detected in model group，CTX group and combination groups，and the contents of
MDA，SOD and GSH，the levels of VEGF，TNF-α and IL-6 in the tumor tissue were detected by colorimetry and ELISA in above
groups. The protein expression of oncogenes （p53，Bcl-2 and Bax） were detected by immunohistochemical method in model
group，CTX group and CTX+LEM group. RESULTS：The mice in the model group were in poor spirit and had symptoms of
excessive drinking and eating；although the body weight，TI and SI were not significantly abnormal compared with normal group
（P＞0.05），WBC count and AST content were significantly increased，ALT and BUN contents were significantly decreased（P＜
0.05 or P＜0.01）. Compared with model group，above symptoms of mice were all improved in administration groups. The tumor
weight of administration groups，TI and SI of CTX group and TI of combination groups were decreased significantly，but tumor
weight of LEL group and LEH group，TI and SI of LE single groups and combination groups were significantly higher than CTX
group；tumor weight of combination groups were significantly lower than CTX group（P＜0.05 or P＜0.01）. The tumor inhibition
rates of administration groups were 29.58％-72.08％. The q values of CTX+LEL group，CTX+LEM group and CTX+LEH group
were 1.03，0.97 and 0.86，respectively. Compared with model group，WBC count，AST and BUN contents of CTX group，MDA
contents of combination groups，VEGF，TNF-α and IL-6 levels of administration groups，the protein expression of Bcl-2 in CTX
group and CTX+LEM group were decreased significantly；the activities of SOD and GSH of administration groups，the protein
expression of p53 in CTX+LEM group and Bax in CTX group，CTX+LEM group were increased significantly（P＜0.05 or P＜
0.01）；WBC counts and AST contents of administration groups，ALT content of CTX+LEM group，SOD activity of CTX+LEH
group and GSH activity of CTX+LEM group were all significantly higher than those of CTX group；MDA content of CTX+LEH
group，VEGF and TNF-α levels of CTX + LEM group and CTX + LEH group，IL-6 levels of administration groups were all
significantly lower than CTX group（P＜0.05 or P＜0.01）. CONCLUSIONS：LE combined with CTX can increase the anti-tumor
effect，and LE can reduce the toxicity of CTX induced immunosuppression and bone marrow suppression in mice，with effect of
increasing efficacy and decreasing toxicity. The effect may be related to antioxidant stress，inhibition of angiogenesis and secretion
of inflammatory factors，and regulation of apoptosis protein expression.
KEYWORDS Limax extract；Hepatocellular carcinoma；Antioxidant stress；Angiogenesis；Cell apoptosis；Increasing efficacy
and decreasing toxicity；Mice

肝癌（Hepatocellular carcinoma）是目前我国排第 4 （Cyclophosphamide，CTX）是应用最广泛的传统化疗药
位的常见恶性肿瘤及致死病因排第3位的肿瘤。每年新 物之一，但CTX可通过血液循环激活其自身代谢产物丙
发病例超全球肿瘤新发病例总数的一半，严重危害人们 烯醛，从而对机体正常细胞产生毒性作用，如骨髓抑制
的生命健康 [1-2] 。肝癌发病机制复杂，其病因尚未完全阐 和免疫抑制等，治疗效果有限 。研究表明，中药联合化
[3]
明；加之现有化疗药物的安全性欠佳，可能导致患者机 疗药物可提高抗肿瘤疗效和/或减少副作用 [3，6] 。同时，
[3]
体免疫功能下降而使得治疗效果受到影响 。由此可 有研究报道LE联合化疗药物在体外对肝癌细胞具有凋
[7]
见，肝癌的临床治疗仍然面临严峻的挑战，故寻找有效、 亡诱导作用 。为进一步探索LE的体内抗肝癌作用，本
安全的肝癌治疗药物备受学者关注。 研究通过建立 H22 荷瘤小鼠模型，研究 LE 对 CTX 治疗
蛞蝓 Agriolimax agrestis L.属软体动物门腹足纲柄 肝癌的增效减毒作用，旨在为临床抗肝癌联合药物方案
眼目蛞蝓科，因其形似蜗牛却无壳，浑身黏液，故俗称为 的选择提供参考。
“鼻涕虫”。研究表明，蛞蝓虫体中含有多糖类和蛋白类 1 材料
活性成分，其活性提取物对肺腺癌细胞A549、肉瘤细胞 1.1 仪器
S180、宫颈癌细胞 HeLa 等均具有较好的体内外抑制作 Spectra Max Plus 384型酶标仪（香港分子仪器有限
用，且毒性较低 [4-5] 。本课题组前期研究发现，蛞蝓提取 公司）；TU-180 型紫外-可见分光光度计（北京普析通用
物（Limax extract，LE）可抑制肝癌细胞H22的生长，具有 仪器有限责任公司）；CKX41型倒置显微镜（日本Olym-
一定的开发价值。 pus 公司）；7100 型全自动生化分析仪（日本 Hitachi 公
化疗是目前临床治疗肿瘤的主要手段，环磷酰胺 司）；XT-2000I 型血细胞分析仪（日本 Sysmex 公司）；

·18 · China Pharmacy 2021 Vol. 32 No. 1 中国药房 2021年第32卷第1期