雷公藤甲素对裸鼠胰腺癌皮下移植瘤生长的抑制作用及其机制

doi:10.13481/j.1671-587x.20190204

摘要/Abstract

摘要： 目的：观察雷公藤甲素对人胰腺癌荷瘤裸鼠的抑瘤作用，探讨其作用的分子机制。方法：选择健康BALB/c裸鼠于右后肢皮肤移植人胰腺癌SW1990细胞，建立裸鼠荷瘤模型，将建模成功的裸鼠分为模型组、吉西他滨组和雷公藤甲素组，每组10只，另选10只健康裸鼠作为对照组。测量各组SW1990胰腺癌荷瘤裸鼠体质量，取肿瘤组织称质量，计算肿瘤抑制率；采用免疫组织化学法检测各组裸鼠胰腺组织中凋亡相关蛋白Bax和Bcl-2的表达情况；采用Western blotting法检测各组裸鼠胰腺组织中凋亡相关蛋白Bax、Bcl-2、Caspase-9和Caspase-3表达水平。结果：与吉西他滨组比较，雷公藤甲素组SW1990胰腺癌的肿瘤抑制率明显升高（P<0.05）。HE染色观察，与模型组比较，雷公藤甲素组裸鼠胰腺癌肿瘤细胞增殖受到抑制。免疫组织化学检测，与模型组比较，雷公藤甲素组裸鼠胰腺组织中Bcl-2表达水平和Bcl-2/Bax比值明显降低（P<0.05）。Western blotting法检测，与模型组比较，雷公藤甲素组裸鼠胰腺组织中Bax、Caspase-9和Caspase-3蛋白表达水平均明显升高（P<0.05），而Bcl-2蛋白表达水平明显降低（P<0.05）。结论：雷公藤甲素能抑制裸鼠肿瘤组织的生长，其机制可能与抑制胰腺肿瘤组织中Bcl-2的激活、促进Bax的表达、降低Bcl-2/Bax的比值、促使Caspase-9和Caspase-3激活及诱导胰腺癌移植瘤细胞凋亡有关。

关键词: 雷公藤甲素, 人胰腺癌SW1990细胞, 胰腺肿瘤, Bax, Bcl-2, Caspase-9, Caspase-3

Abstract: Objective: To observe the antitumor effect of triptolide in the human pancreatic cancer tumor-bearing nude mice, and to explore its molecular mechanism.Methods: The healthy BALB/c nude mice were selected and transplanted with the human pancreatic cancer SW1990 cells into the skin of the right hind limb to establish the tumor-bearing model of nude mice. The successful modeling nude mice were divided into model group, gemcitabine group and triptolide group, 10 in each group; another 10 healthy nude mice were selected as control group. The tumor tissue of SW1990 pancreatic cancer tumor-bearing nude mice were weighed and the inhibitory rate of tumor was calculated. The expressions of apoptosis-related proteins Bax and bcl-2 in the pancreas tissue of the nude mice in each group were detected by immunohistochemistry. The expression levels of Bax, bcl-2, Caspase-9 and Caspase-3 in the pancreas tissue of the nude mice in each group were detected by Western blotting method.Results: Compared with gemcitabine group, the inhibitory rate of tumor of SW1990 pancreatic cancer in triptolide group was significantly increased(P<0.05). The HE staining results showed that compared with model group, the proliferation of pancreatic cancer tumor cells in triptolide group was inhibited. The immunohistochemistry results showed that the expression level of Bcl-2 in the pancreas tissue and the Bcl-2 /Bax ratio of the nude mice in tripptolide group were lower than those in model group (P<0.05). The Western blotting results showed that compared with model group, the expression levels of Bax, Caspase-9 and Caspase-3 in the pancreas tissue of the nude mice in triptolide group were significantly increased (P<0.05), while the expression level of Bcl-2 was significantly decreased (P<0.05).Conclusion: Triptolide can inhibit the growth of tumor tissue in the nude mice;its mechanism may be related to inhibiting the activation of Bcl-2 in pancreatic tumor tissue, promoting the expression of Bax, reducing the ratio of Bcl-2 /Bax, promoting the activation of Caspase-9 and Caspase-3, and inducing the apoptosis of pancreatic cancer transplanted tumor cells.

Key words: triptolide, human pancreatic cancer SW1990 cells, pancreas neoplasms, Bax, Bcl-2, Caspase-9, Caspase-3

中图分类号:

R285.5

王云检, 张珉, 蒙博, 尤国华, 张璐阳. 雷公藤甲素对裸鼠胰腺癌皮下移植瘤生长的抑制作用及其机制[J]. 吉林大学学报(医学版), 2019, 45(02): 234-238.

WANG Yunjian, ZHANG Min, MENG Bo, YOU Guohua, ZHANG Luyang. Inhibitory effect of triptolide on growth of subcutaneous tumor of pancreatic cancer in nude mice and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2019, 45(02): 234-238.

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