氯喹对S180荷瘤小鼠的抑瘤作用及其机制

岳丽玲* 梅庆步 朱文斌 张微 刘得水 刘莹

doi:10.16098/j.issn.0529-1356.2016.06.010

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解剖学报 ›› 2016, Vol. 47 ›› Issue (6) : 779-784. DOI: 10.16098/j.issn.0529-1356.2016.06.010

肿瘤生物学

氯喹对S₁₈₀荷瘤小鼠的抑瘤作用及其机制

岳丽玲^1* 梅庆步² 朱文斌¹ 张微¹ 刘得水¹刘莹³

作者信息 +

Anti-tumor effects of chloroquine on S₁₈₀tumor-bearing mice and its mechanisms

YUE Li-ling ^1* MEI Qing-bu² ZHU Wen-bin¹ ZHANG Wei¹ LIU De-shui¹ LIU Ying³

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文章历史 +

摘要

目的探讨氯喹（CQ)对小鼠移植性肉瘤S180的抑瘤作用及其可能机制。方法采用40只S₁₈₀荷瘤小鼠分为模型组，氯喹低剂量组，氯喹中剂量组，氯喹高剂量组进行体内抑瘤实验，观察不同浓度氯喹对小鼠肉瘤S₁₈₀的抑制作用；透射电子显微镜观察氯喹作用下荷瘤鼠肿瘤细胞超微结构的变化；流式细胞术检测氯喹诱导荷瘤鼠S₁₈₀细胞凋亡的情况；免疫组织化学方法检测相关凋亡因子Bcl-2、细胞色素C和Cle0-Caspase-3的表达情况；Western blotting检测荷瘤组织Bcl-2和Cle-Caspase-3蛋白表达水平的变化以及线粒体和细胞质中细胞色素C蛋白含量的变化。结果与模型组相比较，氯喹处理组小鼠移植肉瘤S₁₈₀生长速度显著减慢，肿瘤体积和瘤质量明显减小（P<0.05）；透射电子显微镜观察发现，与模型组比较氯喹处理组肿瘤细胞形态出现明显凋亡损伤改变，凋亡小体形成；各剂量组氯喹均可诱导荷瘤鼠S₁₈₀细胞凋亡，使抗凋亡因子Bcl-2表达下调，凋亡因子Cle-Caspase-3表达上调（P<0.05）；并且氯喹能够降低线粒体内细胞色素C蛋白的表达，提高细胞质细胞色素C蛋白的表达（P<0.05），促使线粒体内细胞色素C向细胞质内释放。结论氯喹能够抑制小鼠S₁₈₀肉瘤的生长，可能是通过线粒体凋亡途径诱导细胞凋亡，从而发挥抑瘤的作用。

Abstract

Objective To investigate the anti-tumor function of chloroquine on bearing cancer mice S₁₈₀ and its possible mechanism. Methods Forty S₁₈₀ tumor-bearing mice were divided into chlorquine, low dose group, middle dose and high dose group. The inhibiting effect of different concentration chloroquine on sarcoma 180 was observed with in vivo. The morphological changes in tumor cells of tumorbearing mice induced by chloroquine was observed under the transmission electron microscope. The apoptosis of tumor cells induced by chloroquine were tested with flow cytometry. The expression of apoptosisrelated factors Bcl-2, cytochrome-C and Cle-Caspase-3 was detected by immunohistochemistry. Western blotting was used to detect the protein levels of Bcl-2, Cle-Caspase-3 in tissue and the changes of Cytochrome-C in mitochondria and cytoplasm. Results Compared with the control group, the growth rate, the xenon graft volume and weight decreased obviously in chloroquine group (P<0.05). Apoptotic changes and apoptotsis body were discovered obviously in chloroquine group under the electron microscope. Chloroquine induced the apoptosis of bearing cancer mice S₁₈₀cell in every group, down-regulated the expression of anti-apoptotic factors Bcl-2 and up-regulated the expression of apoptotic genes Cle-Caspase-3 (P<0.05). Chloroquine reduced the mitochondria Cytochrome-C protein levels and increased the cytoplasm cytochrome-C protein levels (P<0.05). Chloroquine promoted the release of cytochrome-C to cytoplasm. Conclusion Chloroquine has the anti-tumor effect on the growth of bearing cancer mice S180 cell. It may affect the mitochondria apoptosis pathway and thus play a role in anti-tumor.

导出引用

岳丽玲梅庆步朱文斌张微刘得水刘莹. 氯喹对S₁₈₀荷瘤小鼠的抑瘤作用及其机制[J]. 解剖学报. 2016, 47(6): 779-784 https://doi.org/10.16098/j.issn.0529-1356.2016.06.010

YUE Li-ling MEI Qing-bu ZHU Wen-bin ZHANG Wei LIU De-shui LIU Ying. Anti-tumor effects of chloroquine on S₁₈₀tumor-bearing mice and its mechanisms[J]. Acta Anatomica Sinica. 2016, 47(6): 779-784 https://doi.org/10.16098/j.issn.0529-1356.2016.06.010

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