超声联合紫杉醇对乳腺癌裸鼠病理学形态、生物学特性及肿瘤抑制的影响

Effect of Ultrasound Combined with Paclitaxel on Pathological Morphology,Biological Characteristics and Tumor Inhibition in Nude Mice with Breast Cancer

目的探讨超声联合紫杉醇对乳腺癌裸鼠病理学形态、生物学特性及肿瘤抑制的影响。方法选取健康裸鼠50只,分为健康组(A组)、模型组(B组)、超声组(C组)、紫杉醇组(D组)、联合组(CD组),每组各10只,除健康组外均建立乳腺癌模型,建模后A组、B组行生理盐水腹腔注射;C组用超声波辐射治疗;D组采用经腹腔内注射紫杉醇注射液;CD组在超声引导下经腹腔内多点注射20 mg/kg/w紫杉醇注射液。测量肿瘤体积,TUNEL检测乳腺癌细胞凋亡,HE染色观察病理学形态,免疫印迹检测半胱氨酸蛋白酶Caspase-3、Caspase-2和B淋巴细胞Bax、Bcl-2蛋白表达。结果经超声显示,B组裸鼠肿瘤体积较大;C组、D组肿瘤体积轻度增大,可见液化坏死;CD组肿瘤体积增长减缓,周边可检测到血流信号。HE染色显示,A组裸鼠无病变现象;B组裸鼠组织结构坏死严重;C组、D组裸鼠癌组织仍有浸润性生长现象;CD组可见少量变性坏死,及组织分布少量残存癌组织,细胞轮廓逐渐稳定。与B组比较,C组、D组肿瘤体积减小(P<0.05);与C组、D组比较,CD组肿瘤体积减小(P<0.05)。与A组比较,B组乳腺癌细胞凋亡增加(P<0.05);与B组比较,C组、D组乳腺癌细胞凋亡增加(P<0.05);与C组、D组比较,CD组乳腺癌细胞凋亡增加(P<0.05)。与A组比较,B组Caspase-3、Caspase-2、Bax降低,Bcl-2升高(P<0.05);与B组比较,C组、D组Caspase-3、Caspase-2、Bax升高,Bcl-2降低(P<0.05);与C组、D组比较,CD组Caspase-3、Caspase-2、Bax升高,Bcl-2降低(P<0.05)。结论超声联合紫杉醇可抑制乳腺癌裸鼠肿瘤生长、促进癌细胞凋亡,与上调肿瘤组织中Caspase-3、Caspase-2、Bax蛋白表达,抑制Bcl-2活性相关。

Objective To investigate the effects of ultrasound combined with paclitaxel on pathological morphology,biological characteristics and tumor inhibition innude mice with breast cancer.Methods A total of 50 healthy nude mice were selected and divided into healthy group(group A),model group(group B),ultrasound group(group C),paclitaxel group(group D)and combination(group CD),with 10 mice in each group.Breast cancer model was established except for healthy group.After modeling,nude mice in group A and group B were intraperitoneally injected with normal saline.The nude mice in group C were treated with ultrasonic radiation.Group D was given paclitaxel injection intraperitoneally.In group CD,20 mg/kg/w paclitaxel injection was added into the skin under ultrasound guidance.The tumor volume was observed and measured,the apoptosis of breast cancer cells was detected by TUNEL,pathological morphology was observed by HE staining,and protein expressions of cysteine proteases Caspase-3 and Caspase-2 and Bax and Bcl-2 in B lymphocytes were detected by western blots.Result Ultrasound showed that the tumor volume in group B was larger.In group C and group D,the tumor volume was slightly increased and liquefaction necrosis was observed.In group CD,the volume of swelling increased slowly,and blood flow signal could be detected in the periphery.HE staining showed that the nude mice in group A had no lesions;the tissue structure of nude mice in group B was severely necrotic;the tumor tissues of nude mice in groups C and D still showed invasive growth;in the group CD,a small amount of degeneration and necrosis were observed,and a small amount of residual cancer tissue was distributed,and the cell profile was gradually stable.Compared with group B,the tumor volume in groups C and D was decreased(P<0.05);and compared with groups C and D,the tumor volume in group CD was decreased(P<0.05).Compared with group A,the apoptosis of breast cancer cells in group B was increased(P<0.05);compared with group B,the apoptosis of breast cancer cells in groups C and D was increased(P<0.05);and compared with groups C and D,the apoptosis of breast cancer cells in group CD was increased(P<0.05).Compared with group A,Caspase-3,Caspase-2 and Bax were decreased and Bcl-2 was increased in group B(P<0.05);compared with group B,Caspase-3,Caspase-2,Bax were increased and Bcl-2 was decreased in groups C and D(P<0.05);and compared with groups C and D,Caspase-3,Caspase-2 and Bax were increased,while Bcl-2 was decreased in group CD(P<0.05).Conclusion Ultrasound combined with paclitaxel can inhibit tumor growth and promote cancer cell apoptosis in nude mice with breast cancer,which is related to upregulation of Caspase-3,Caspase-2 and Bax protein expression in tumor tissue and inhibition of Bcl-2 activity.