首页|龙胆苦苷联合帕博利珠单抗在乳腺癌荷瘤小鼠光动力治疗中的协同作用

龙胆苦苷联合帕博利珠单抗在乳腺癌荷瘤小鼠光动力治疗中的协同作用

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目的 研究龙胆苦苷联合帕博利珠单抗在乳腺癌荷瘤小鼠光动力治疗中的协同作用.方法 用皮下注射MCF-7细胞建立乳腺癌荷瘤小鼠模型,并随机分为模型组、对照组、阳性对照组、实验组和联合组,每组10只.对照组腹腔注射50 mg·kg-1 5-氨基酮戊酸,每周1次,12 h后以200 J·cm-2激光照射20 min,每周1次.在对照组治疗的基础上,阳性对照组腹腔注射100 pig·kg-1帕博利珠单抗,每周2次;实验组灌胃给予100 mg·kg-1龙胆苦苷,每天1次;联合组腹腔注射100 μg·kg-1帕博利珠单抗,每周2次+灌胃给予100 mg·kg-1龙胆苦苷,每天1次;模型组腹腔注射0.9%NaCl,每天1次.5组小鼠均连续给药3周.比较各组小鼠的肿瘤抑制率,用酶联免疫吸附试验法测定白细胞介素(IL)-12、干扰素(INF)-γ和肿瘤坏死因子(TNF)-α水平,用蛋白质印迹法测定肿瘤组织中B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)和血管内皮生长因子(VEGF)蛋白的表达水平.结果 对照组、阳性对照组、实验组和联合组的肿瘤抑制率分别为(22.38±2.26)%、(42.27±3.21)%、(38.16±2.17)%和(60.24±2.84)%;模型组、对照组、阳性对照组、实验组和联合组的血清IL-12分别为(127.13±1.25)、(132.29±2.31)、(155.27±1.48)、(163.31±2.67)和(185.24±1.71)pg·mL-1,INF-γ 分别为(724.16±3.63)、(891.12±4.45)、(1 043.19±3.85)、(1 082.34±4.51)和(1 492.13±6.57)pg·mL-1,TNF-α 分别为(83.81±4.52)、(65.26±3.77)、(41.07±3.85)、(43.59±3.94)和(27.12±3.93)pg·mL-1,Bcl-2 蛋白相对表达水平分别为0.99±0.04、0.86±0.06、0.71±0.05、0.46±0.06 和 0.31±0.08,Bax 蛋白相对表达水平分别为 0.30±0.08、0.47±0.05、0.67±0.11、0.89±0.06 和1.03±0.10,VEGF 蛋白相对表达水平分别为 1.06±0.04、0.92±0.03、0.76±0.04、0.49±0.04和0.29±0.08.联合组的上述指标与对照组、阳性对照组、实验组相比,在统计学上差异均有统计学意义(均P<0.05).结论 龙胆苦苷联合帕博利珠单抗能够显著增强光动力疗法对乳腺癌小鼠的肿瘤抑制作用,促进乳腺癌细胞凋亡,进而抑制乳腺癌小鼠的肿瘤进展.
Synergistic effects of gentiopicroside combined with pabolizumab on photodynamic treatment of breast cancer mice
Objective To study the synergistic effects of gentiopicroside combined with pabolizumab on photodynamic therapy in mice with breast cancer.Methods MCF-7 cells were injected subcutaneously to establish a tumor bearing mouse model of breast cancer and were randomly divided into model group,control group,positive control group,experimental group and combination group,with 10 mice in each group.The control group was intraperitoneally injected with 50 mg·kg-1 of 5-aminolevulinic acid and irradiated with 200 J·cm-2 laser for 20 min,once a week.The positive control group was intraperitoneally injected with 100μg·kg-1 pabolizumab,twice a week,and photodynamic therapy once a week,the experimental group was intragastric given 100 mg·kg-1 gentiopicroside,once a day,and photodynamic therapy once a week,the combined group was intraperitoneally injected with pabolizumab(100 μg·kg-1),twice a week,and gavage of gentiopicroside(100 mg·kg-1)once a day and photodynamic therapy once a week.Five groups of mice were given the drug for 3 weeks.The tumor inhibition rate of each group was compared,and the levels of interleukin(IL)-12,interferon(INF)-γand tumor necrosis factor(TNF)-α were measured by enzyme-linked immunosorbent assay.The levels of B-cell lymphoma-2 associated gene(Bax),B-lymphoblastoma-2 gene(Bcl-2)and vascular endothelial growth factor(VEGF)protein in tumor tissues were determined by Western blot.Results The tumor inhibition rates of control,positive control,experimental and combined groups were(22.38±2.26)%,(42.27±3.21)%,(38.16±2.17)%and(60.24±2.84)%,respectively.The serum IL-12 levels of model,control,positive control,experimental and combined groups were(127.13±1.25),(132.29±2.31),(155.27±1.48),(163.31±2.67)and(185.24±1.71)pg·mL-1;INF-γ levels were(724.16±3.63),(891.12±4.45),(1 043.19±3.85),(1 082.34±4.51)and(1 492.13±6.57)pg·mL-1;TNF-α levels were(83.81±4.52),(65.26±3.77),(41.07±3.85),(43.59±3.94)and(27.12±3.93)pg·mL-1;the relative protein expression levels of Bax were 0.30±0.08,0.47±0.05,0.67±0.11,0.89±0.06 and 1.03±0.10;the relative protein expression levels of Bcl-2 were 0.99±0.04,0.86±0.06,0.71±0.05,0.46±0.06 and 0.31±0.08;the relative protein expression levels of VEGF were 1.06±0.04,0.92±0.03,0.76±0.04,0.49±0.04 and 0.29±0.08.The differences of above indexes between the combined group and the control,positive control group and experimental groups were statistically significant(all P<0.05).Conclusion Gentiopicroside combined with pembrolizumab can significantly enhance the tumor inhibition effect of photodynamic therapy on breast cancer mice,promote the apoptosis of breast cancer cells,and then inhibit the tumor progression of breast cancer mice.

gentiopicrosidepembrolizumabmonoclonal antibodybreast cancerphotodynamic therapy

冯劼妮、郭超凡、林华隆、原少斐

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瑞安市人民医院肿瘤内科,浙江瑞安 325200

瑞安市人民医院骨科,浙江瑞安 325200

龙胆苦苷 帕博利珠单抗 光动力治疗 乳腺癌

浙江省中医药科技计划温州市科技局项目

2023ZL170Y2020742

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(2)
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