黄连素对乳腺癌大鼠的治疗作用

Therapeutic effect of berberine on breast cancer in rats

目的探讨黄连素对乳腺癌大鼠的治疗作用及可能机制。方法雌性SD大鼠60只,随机分为对照组10只和实验组50只。实验组给予二甲基苯蒽悬浮液100mg/kg灌胃制备乳腺癌大鼠模型,对照组给予等体积橄榄油灌胃。灌胃13周时对照组处死1只、实验组处死5只大鼠观察造模是否成功。模型制备成功后,将实验组45只大鼠分为模型组,黄连素低、中、高剂量组和三氧苯胺组各9只,分别给予体积分数0.1%羧甲基纤维素10mL/kg、黄连素100mg/kg、黄连素200mg/kg、黄连素300mg/kg、三氧苯胺5.6mg/kg灌胃,1次/d,连续8周。8周后测量肿瘤体积并计算肿瘤细胞数量;采用ELISA法检测血清白细胞介素(interleukin,IL)-4、IL-10、IL-12、γ-干扰素(interferon-γ,IFN-γ)水平。结果对照组镜下未见肿瘤细胞,黄连素低、中、高剂量组和三氧苯胺组肿瘤细胞数量[(1.9±0.6)、(1.7±0.7)、(1.6±0.5)、(1.6±0.5)个]较模型组[(2.5±0.5)个]少,肿瘤体积[(2.61±0.37)、(2.56±0.25)、(2.35±0.32)、(2.31±0.40)cm3]较模型组[(3.06±0.53)cm3]小(P<0.05);三氧苯胺组及黄连素低、中、高剂量组肿瘤细胞数量及肿瘤体积比较差异均无统计学意义(P>0.05);模型组及黄连素低、中、高剂量组和三氧苯胺组IL-12[(20.82±1.75)、(22.74±1.61)、(23.25±1.01)、(25.18±1.33)、(23.80±1.13)ng/L]、IFN-γ[(16.42±1.01)、(19.31±1.04)、(22.83±1.05)、(23.22±0.88)、(23.84±1.60)ng/L]水平均低于对照组[(28.88±2.06)、(27.32±1.26)ng/L](P<0.05),黄连素低、中、高剂量组和三氧苯胺组IL-12、IFN-γ水平高于模型组(P<0.05);模型组及黄连素低、中、高剂量组和三氧苯胺组IL-4[(116.29±2.84)、(109.19±4.48)、(98.76±3.02)、(95.50±4.77)、(97.10±4.58)ng/L]、IL-10[(57.70±5.98)、(42.50±4.28)、(43.70±3.09)、(40.20±2.66)、(42.90±1.97)ng/L]水平均高于对照组[(91.85±2.26)、(36.57±3.55)ng/L](P<0.05);黄连素低、中、高剂量组和三氧苯胺组IL-4、IL-10水平低于模型组(P<0.05);三氧苯胺组及黄连素低、中、高剂量组IL-12、IFN-γ、IL-4、IL-10水平比较差异均无统计学意义(P>0.05)。结论黄连素可能通过促进血清IFN-γ、IL-12表达,抑制血清IL-4、IL-10表达来抑制乳腺癌细胞的生长。

Objective To explore the therapeutic effect of berberine on breast carcinoma in rats.Methods Sixty female SD rats were randomly divided into control group and experimental group,with 50 rats in each group.Experimental group was given gavage by 100 mg/kg dimethyl benzene anthracene suspension to prepare breast cancer rat model.Control group was given gavage by equivalent volume of olive oil.After the model was successfully prepared,experimental group was divided into model group,berberine low-,medium-and high-dose groups,and tamoxifen group,with 9rats in each group,receiving 10 mL/kg carboxymethyl cellulose,100 mg/kg berberine,200 mg/kg berberine,300mg/kg berberine and 5.6mg/kg trioxanil,once a day,totally for 8weeks,respectively.After 8weeks,the tumor volumes were measured,and the tumor cell counts were calculated.The contents of interleukin(IL)-4,IL-10,IL-12 and interferon-γ(IFN-γ)in serum were measured by ELISA.Results No tumor cells were found in control group.The tumor cell count was significantly less in berberine low-dose group,berberine medium-dose group,berberine high-dose group and tamoxifen group(1.9±0.6,1.7±0.7,1.6±0.5,1.6±0.5),and the tumor volume was significantly smaller in berberine low-dose group,berberine medium-dose group,berberine high-dose group and tamoxifen group((2.61±0.37),(2.56±0.25),(2.35±0.32),(2.31±0.40)cm3)than those in model group(2.5±0.5,(3.06±0.53)cm3)(P<0.05).There were no significant differences in tumor cell count and tumor volume among trioxanil group,berberine low-dose group,berberine medium-dose group and berberine high-dose group(P>0.05).The expressions of IL-12((20.82±1.75),(22.74±1.61),(23.25±1.01),(25.18±1.33),(23.8±1.13)ng/L)and IFN-γ((16.42±1.01),(19.31±1.04),(22.83±1.05),(23.22±0.88),(23.84±1.60)ng/L)in model group,berberine low-dose group,berberine medium-dose group,berberine high-dose group and tamoxifen group were significantly lower than those in control group((28.88±2.06),(27.32±1.26)ng/L)(P<0.05),and were significantly higher in berberine low-dose group,berberine medium-dose group,berberine high-dose group and tamoxifen group than those in model group(P<0.05).The expressions of IL-4((116.29±2.84),(109.19±4.48),(98.76±3.02),(95.50±4.77),(97.10±4.58)ng/L)and IL-10((57.70±5.98),(42.50±4.28),(43.70±3.09),(40.20±2.66),(42.90±1.97)ng/L)in model group,berberine low-dose group,berberine medium-dose group,berberine high-dose group and tamoxifen group were significantly higher than those in control group((91.85±2.26),(36.57±3.55)ng/L)(P<0.05),and were significantly lower in berberine low-dose group,berberine medium-dose group,berberine high-dose group and tamoxifen group than those in model group(P<0.05).There were no significant differences in the expressions of IL-12,IFN-γ,IL-4and IL-10 in berberine low-dose group,berberine medium-dose group,berberine high-dose group and tamoxifen group(P>0.05).Conclusion Berberine can inhibit the growth of breast cancer cells by promoting the expressions of IFN-γand IL-12,and inhibiting the expressions of IL-4and IL-10.