[摘 要] 目的：探讨碱性亮氨酸拉链转录因子ATF样蛋白3（BATF3）在肾透明细胞癌（ccRCC）组织中的表达及其调控ccRCC细胞恶性生物学行为的分子机制。方法：收集2019年3月至2022年1月间在中国人民解放军联勤保障部队第九八〇医院手术切除的64例ccRCC组织和相应癌旁组织，qPCR法检测ccRCC组织、癌旁组织和肾癌ACHN、786-O细胞中BATF3 mRNA的表达，免疫组化检测ccRCC组织、癌旁组织中BATF3蛋白的表达，并分析其与临床病理特征的关系。构建BATF3敲减及过表达质粒，分别转染786-O、ACHN细胞，通过MTS法、Transwell实验检测BATF3对786-O或ACHN细胞增殖、迁移、侵袭能力的影响，qPCR法检测敲减或过表达BATF3对786-O或ACHN细胞EMT相关基因表达的影响，CHIP、双荧光素酶报告基因实验检测BATF3是否与波形蛋白（VIM）启动子区结合并调控其转录，MTS法、Transwell实验检测同时过表达BATF3及敲减VIM对786-O细胞增殖、迁移、侵袭能力的影响。结果：与癌旁组织比较，ccRCC组织中BATF3的mRNA和蛋白均呈高表达(均P<0.01)，并且BATF3 mRNA与ccRCC的分化程度和TNM分期密切关联（均P<0.01）；与正常肾上皮细胞293T相比，BATF3在ACHN及786-O细胞中均呈高表达（均P<0.01）。敲减BATF3表达均能明显抑制786-O细胞的增殖、迁移、侵袭能力(均P<0.01)，过表达BATF3则均能促进ACHN细胞的增殖、迁移和侵袭能力（均P<0.01），敲减或过表达BATF3能抑制786-O细胞或促进ACHN细胞的EMT相关基因的表达（均P<0.01）。BATF3可与VIM启动子区的位点结合，直接调控VIM的转录表达。同时过表达BATF3及敲减VIM可逆转过表达BATF3对786-O细胞增殖、迁移、侵袭能力的影响。结论：BATF3在ccRCC组织中呈高表达，并与其分化程度和TNM分期密切关联；BATF3通过调控VIM的表达影响ACHN、786-O细胞的恶性生物学行为，其可作为临床治疗ccRCC的潜在靶点。

Objective: To explore the difference in the proliferation inhibition of doxorubicin and dual specific oncolytic adenoviruses (Ad-VT, Ad-T, Ad-VP3 and d-Mock) on breast cancer cells and normal mammary cells. Methods: The proliferation inhibition rates of doxorubicin and recombinant adenovirus(Ad-VT, Ad-T, Ad-VP3and Mock) on breast cancer cells were detected through WST-1 experiment, and the effects of two drugs on the inhibitory rates of normal mammary epithelial cells were also detected. Moreover, the apoptosis rates of doxorubicin and oncolytic adenoviruses on breast cancer cells and normal mammary epithelial cells were evaluated by Annexin V flow cytometry, Hoechst and JC-1 staining, and the difference in the apoptosis rates were also compared. Results: All the recombinant adenovirus could effectively suppress the proliferation of breast cancer cells (P<0.05 or P<0.01), the inhibition effects followed the order ofAd-VT>Ad-T>Ad-VP3>Ad-MOCK, and the inhibition effect was positively correlated with time. Doxorubicin could also effectively suppress the proliferation of breast cancer cells (P<0.05 or P<0.01), and the inhibition effect was markedly enhanced with the increases in does and time. However, doxorubicin also showed strong inhibition effect on the normal mammary epithelial cells, and the inhibition rate achieved 80% under 72 h and 5 ug/ml doxorubicin, while that of oncolytic adenovirus Ad-VT on MCF-10A was 20% at 72 h. The apoptosis effects of oncolytic adenoviruses-induced breast cancer cellwere increased with time, and the apoptosis rate efficiency followed the order of Ad-VT>Ad-T>Ad-VP3>Ad-MOCK, but they displayed low ability to induce normal mammary cell apoptosis. The apoptosis effects of doxorubicin-induced breast cancer cell were similar to that of the normal mammary epithelial cell (P <0.05 or P<0.01), which followed the dose of 0.05<0.5<5 μg/ml. Conclusion: Dual specific oncolytic adenoviruses can effectively suppress the proliferation of breast cancer cells, but they have low inhibition on normal mammary cells, which have displayed superior safety and provide a new method for the biotherapy of tumor.