首页|DM-[Ch][Tau]对小鼠H22肝癌移植瘤的抑制作用

DM-[Ch][Tau]对小鼠H22肝癌移植瘤的抑制作用

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目的 研究5,6-二溴去甲斑蝥素单酸甲酯(DM)-牛磺酸胆碱离子液体([Ch][Tau],DM-[Ch][Tau])瘤内注射对小鼠H22 肝癌移植瘤的抑制作用。方法 采用CCK-8 法评价DM、[Ch][Tau]及联用体外抗H22 肝癌细胞活性。皮下接种H22 肝癌细胞构建移植瘤小鼠模型,将25 只BALB/c荷瘤小鼠随机分为模型组(生理盐水)、[Ch][Tau]组、NCTD组(去甲斑蝥素)、DM组和DM-[Ch][Tau]组,每2 日给药 1 次,连续给药治疗 1 周,观察小鼠及其皮下移植瘤生长情况,计算体重、瘤体积、瘤重和抑瘤率。HE染色观察肿瘤组织病理形态,TUNEL检测肿瘤细胞凋亡,免疫组化染色检测瘤组织BAX、Bcl-2的表达。结果 DM、[Ch][Tau]对H22 增殖均具有抑制作用,IC50 分别为 1。13 和 234。30 μg/mL,DM和[Ch][Tau]联用对H22 的抑制作用强于DM,DM-[Ch][Tau]([Ch][Tau]浓度=300 μg/mL)IC50 为 0。84 μg/mL。与模型组相比,[Ch][Tau]组、NCTD组、DM组、DM-[Ch][Tau]组的抑瘤率是 6。81%、27。82%、39。07%、64。55%;[Ch][Tau]组小鼠肿瘤在给药后仍迅速增长,NCTD组与DM组肿瘤生长速度缓慢,有一定抑制作用,DM-[Ch][Tau]组小鼠肿瘤生长受到显著抑制,肿瘤组织消融坏死,肿瘤生长显著低于模型组(P<0。05)。各组肿瘤组织均局部可见坏死,坏死面积DM-[Ch][Tau]>DM组>NCTD组>模型组。[Ch][Tau]组、模型组、NCTD组、DM组、DM-[Ch][Tau]组的细胞凋亡率为(17。66±13。31)%、(1。05±1。32)%、(26。31±11。89)%、(46。97±19。18)%、(52。85±24。737)%。各组对肿瘤组织中凋亡基因Bax蛋白均有一定的激活作用,DM-[Ch][Tau]组Bax/Bcl-2 的比值最高,肿瘤细胞凋亡作用最强。结论 DM-[Ch][Tau]注射剂对H22肝癌移植瘤小鼠具有明显的抗肿瘤作用,为DM-[Ch][Tau]注射剂制剂研发提供实验数据。
Antitumor effect of DM-[Ch][Tau]in the treatment of transplanted H22 liver cancer in mice
Objective To investigate the inhibitory effect of 5,6-Dibromonorcantharidin Monoeste(DM)and ionic liquid choline-taurinate([Ch][Tau])on H22 hepatocellular carcinoma transplant tumor in mice.Methods CCK-8 was used to assess the impact of DM,[Ch][Tau],and their combination on H22 hepatocellu-lar carcinoma cells.Subcutaneous inoculation of H22 cells was used to establish a mouse model of transplantation tumors.The 25 BALB/c tumor-bearing mice was randomly divided into the model(Saline),[Ch][Tau],Nor-cantharidine,DM,and DM-[Ch][Tau]groups.The medication was given every other day for one week,and body weight and transplanted tumors were observed.The tumor volume,tumor weight,and tumor suppression rate were calculated.Tumor tissue was examined using HE staining,and fluorescent TUNEL staining was per-formed to detect apoptosis.Immunohistochemical staining was performed to determine the expression of Bax and Bcl-2 in tumors.Results DMand[Ch][Tau]showed inhibitory effects on the proliferation of H22 cells,with IC50 of 1.13 μg/mL and 234.30 μg/mL respectively,and DM-[Ch][Tau](300 μg/mL)showed stronger in-hibition than DM,with IC50 of 0.84 μg/mL.Compared with the model group,the tumor suppression rates in[Ch][Tau],Norcantharidine,DM,and DM-[Ch][Tau]groups were 6.81%,27.82%,39.07%,64.55%,respectively.Tumors of[Ch][Tau]group grew rapidly after the administration of the drug.Tumors in Norcan-tharidine and DMgroups grew slowly with some inhibition.Tumor growth in the DM-[Ch][Tau]group was sig-nificantly inhibited,with extensive necrosis of tumors,and tumor growth was significantly lower.Spotty necrosis of tumors was visible in all groups,and the necrotic areas were DM-[Ch][Tau]>DM>Norcantharidine>[Ch][Tau]>model.Apoptosis rates were(17.66±13.31)%,(1.05±1.32)%,(26.31±11.89)%,(46.97±19.18)%,and(52.85±24.737)%in[Ch][Tau],model,Norcantharidine,DM,and DM-[Ch][Tau]groups,respectively.All groups induced apoptotic gene Bax to various extents,and the ratio of Bax/Bcl-2 was the highest in DM-[Ch][Tau]group,with the strongest apoptosis effect on tumor cells.Conclusion DM-[Ch][Tau]injection demonstrated anti-tumor effects in H22 hepatocellular carcinoma-bearing mice,providing evidence for the development of DM-[Ch][Tau]injection in chemotherapy.

brominated norcantharidinionic liquidstransplantation tumorH22 hepatocellular carcinoma

江玲、欧水平、赵长阔、何雅韵、胡荣誉、杨松烨、王森

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遵义医科大学 药学院药剂学教研室,贵州 遵义 563006

遵义医科大学附属医院 药剂科,贵州 遵义 563000

遵义医科大学 药学院药物化学教研室,贵州 遵义 563006

溴代去甲斑蝥素单酸甲酯 离子液体 移植瘤 H22肝癌

遵义市科技计划资助项目遵义医科大学"医技名匠"未来人才培养计划项目

遵市科合HZ字202161号20221040

2024

遵义医科大学学报
遵义医科大学

遵义医科大学学报

CSTPCD
ISSN:2096-8159
年,卷(期):2024.47(7)
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