| 摘要: |
| 目的：探讨超声靶向微泡破坏(ultrasound targeted microbubble destruction, UTMD)介导的整合素亚基a3(integrin subunit a3, ITGA3)转染对乳腺癌生长和上皮间质转化(epithelial interstitial transformation, EMT)的影响。方法：在GEPIA和TCGA数据库中评估ITGA3在乳腺癌中的表达及其与预后的关联；分别使用脂质体或UTMD介导的ITGA3过表达质粒转染人乳腺癌细胞株BT-549细胞；电子显微镜观察细胞形态,MTT法检测细胞活力,划痕实验检测细胞迁移,Transwell小室实验检测细胞侵袭；western blot实验测定ITGA3、E-cadherin、N-cadherin、Vimentin、STAT3、CyclinD1和PCNA的表达；通过裸鼠皮下肿瘤细胞注射法建立裸鼠乳腺癌异种移植瘤模型；免疫组化检测异种移植瘤中ITGA3、N-cadherin和PCNA的表达。结果：ITGA3在乳腺癌组织中的表达明显低于正常组织,ITGA3低表达与乳腺癌患者的不良预后相关；UTMD提高了ITGA3过表达质粒的转染效率；脂质体或UTMD介导的ITGA3过表达质粒均可抑制体外BT-549细胞活力、迁移和侵袭,并延缓异种移植瘤生长；过表达的ITGA3可调节BT-549细胞中EMT相关基因(E-cadherin、N-cadherin、Vimentin)的表达,同时抑制STAT3通路(STAT3、CyclinD1、PCNA)相关蛋白的表达；UTMD介导的ITGA3转染对上述生物学特性的调节作用优于脂质体。结论：UTMD介导的ITGA3过表达质粒转染可有效抑制乳腺癌生长和EMT,为乳腺癌的治疗提供了新的实验证据。 |
| 关键词: 乳腺癌 超声靶向微泡破坏 脂质体 ITGA3 |
| DOI： |
| 投稿时间：2023-09-02修订日期：2024-06-05 |
| 基金项目:2022年度温州市基础性公益科研项目(2022Y0156) |
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| Effect of ultrasound targeted microbubble destruction-mediated ITGA3 on the growth and epithelial-mesenchymal transition of breast cancer |
| Qian Shao-gao,Li zai-li |
| (Ultrasonography department,The affiliated PingYang Hospital of Wenzhou medical university,ZheJiang WenZhou) |
| Abstract: |
| AIM: To investigate the impact of ultrasound-targeted microbubble destruction-mediated transfection of integrin subunit a3 (ITGA3) on the growth and epithelial-mesenchymal transition (EMT) of breast cancer. METHODS: The expression of ITGA3 in breast cancer and its association with prognosis were evaluated by GEPIA and The Cancer Genome Atlas (TCGA) websites. The breast cancer cell line (BT-549) was transfected with liposome- or UTMD-mediated ITGA3 overexpression plasmid, respectively. Cell morphology was observed by electron microscopy. Cell viability was analyzed by MTT assay. Cell migration was detected by the scratch assay. Cell invasion was measured in the transwell chamber assay. The expression of ITGA3, E-cadherin, N-cadherin, Vimentin, STAT3, CyclinD1, and PCNA was detected by western blot. The breast tumor xenograft model was established by subcutaneous tumor cell injection in nude mice, and expression of ITGA3, N-cadherin, and PCNA in xenograft tumors was assessed by immunohistochemistry. RESULTS: The expression of ITGA3 was significantly lower in breast cancer tissues than in normal tissues. Low expression of ITGA3 is associated with poor prognosis in breast cancer patients. UTMD increased the transfection rate of ITGA3. UTMD- and liposome-mediated ITGA3 transfection reduced cell viability, migration, and invasion in BT-549 cells. Ectopic expression of ITGA3 retarded tumor growth in mice. Mechanistically, Overexpression of ITGA3 regulates the expression of EMT-related genes (E-cadherin, N-cadherin, Vimentin) and STAT3 pathway-related factors (STAT3, CyclinD1, PCNA) in BT-549 cells. The regulatory effects of UTMD-mediated ITGA3 transfection on the above-mentioned biological characteristics were better than liposome-mediated ITGA3 transfection. CONCLUSION: UTMD-mediated ITGA3 transfection exerted significant inhibitory effects on the growth and EMT of breast cancer, providing new experimental evidence for the treatment of breast cancer. |
| Key words: breast cancer ultrasound targeted microbubble destruction liposome ITGA3 |
