氯喹对肝癌小鼠肿瘤生长的影响及作用机制

Effect of chloroquine on tumor growth in mice with hepatic carcinoma and its mechanism

目的探讨氯喹对肝癌小鼠肿瘤增殖的影响及其作用机理。方法建立肝癌小鼠肿瘤模型75只,并随机分为对照组、低剂量氯喹处理组和高剂量氯喹处理组,各25只,低剂量和高剂量氯喹处理组小鼠分别腹腔注射不同剂量氯喹(25μmol/L和50μmol/L),对照组注射生理盐水作为对照,连续处理16 d,采用免疫印迹和免疫组化检测3组小鼠肝癌组织中LC3和P62的表达水平,采用MTT法体外检测25μmol/L和50μmol/L浓度的氯喹对Hep G2肝癌细胞增殖活力的影响。结果与对照组相比,氯喹处理组小鼠肝癌组织中LC3(3. 15±0. 29)和P62(6. 24±0. 41)的含量显著增加,阳性细胞率更高,染色强度更深(P <0. 05);Western blot检测结果显示,与对照组比较,LC3和P62的表达水平随氯喹浓度的提高而增加,细胞自噬活性受到抑制(P <0. 05);体外Hep G2肝癌细增殖活性的检测结果显示,较对照组,氯喹处理组肿瘤细胞的增殖活力受到抑制(162. 26±18. 62)%(P <0. 05),呈现时间、剂量依赖性(P <0. 05)。结论氯喹可能通过抑制肿瘤细胞的自噬活性抑制肿瘤细胞的增殖。

Objective To investigate the effect of chloroquine on tumor growth in mice with hepatic carcinoma and the underlying mechanism. Methods The tumor model of liver cancer mice was established, and 75 mice were randomly divided into control group, low-dose chloroquine treatment group, and the high-dose chloroquine treatment group, then the two chloroquine treatment groups were injected with different dose of chloroquine （25 μmol/L and 50 μmol/L）, respectively, and the control group was treated with same amount of saline. After 16 days, the expression of LC3 and P62 in three groups were detected by Western blot and immunohistochemistry, and the proliferation activity of HepG2 treatment with different doses of chloroquine was also analyzed through MTT. Results Compared with control group, the expression of LC3（3.15±0.29） and P62 （6.24±0.41） in chloroquine treatment groups significantly increased, with higher positive cell rate and stronger staining intensity, and the expression of LC3 and P62 also increased with the concentration of chloroquine through Western blot（ P 〈0.05）; besides, the proliferation activity of HepG2 treatment with chloroquine was significantly inhibited（ P 〈0.05）,showing a significant time-and dose-dependent（ P 〈0.05）. Conclusion Chloroquine may promote the apoptosis of tumor or inhibit the proliferation of tumor by inhibiting the autophagic activity of tumor cells.