目的:探讨多柔比星和双特异性溶瘤腺病毒（Ad-VT、Ad-T、Ad-VP3、Ad-Mock）对乳腺癌细胞和正常乳腺细胞增殖抑制作用的差异。方法：通过WST-1 实验比较多柔比星和Ad-VT、Ad-T、Ad-VP3、Ad-Mock对乳腺癌细胞增殖的抑制率，并比较两种药物对正常乳腺上皮细胞的存活率的影响。通过Annexin V流式术、Hoechst 法、JC-1 法检测研究溶瘤腺病毒和多柔比星对乳腺癌细胞和正常乳腺上皮细胞杀伤作用的影响，并比较其凋亡率差异。结果：4 种双特异性溶瘤腺病毒均能有效地抑制乳腺癌细胞的增殖（P<0.05 或P<0.01），且抑制效果为Ad-VT>Ad-T>Ad-VP3>Ad-MOCK，抑制作用与时间成正相关。多柔比星也能有效地抑制乳腺癌细胞的增殖（P<0.05 或P<0.01），且随着浓度和时间的增加，抑制效果明显增强；但多柔比星对正常的乳腺上皮细胞也有较强的抑制作用，在72 h、5 μg/ml 条件下抑制率达到80%，而溶瘤腺病毒Ad-VT在72 h 对MCF-10A的抑制率为20%。双特异性溶瘤腺病毒诱导乳腺癌凋亡能力随时间的增加逐渐增强（P<0.05 或P<0.01），且致凋亡效率为Ad-VT>Ad-T>Ad-VP3>Ad-MOCK，而诱导正常乳腺细胞凋亡能力较弱。多柔比星诱导乳腺癌细胞和正常乳腺上皮细胞凋亡的能力基本相同（P<0.05 或P<0.01），且都为0.05<0.5<5 μg/ml。结论：双特异性溶瘤腺病毒能有效地抑制乳腺癌细胞的增殖，但对正常的乳腺细胞抑制作用较小，双特异性溶瘤腺病毒具有更好的安全性，为肿瘤的生物治疗提供了新的药物。

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 re-combinant adenovirus could effectively suppress the proliferation of breast cancer cells (P<0.05 or P<0.01), the inhibition effects followed the order of Ad-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.

国家重大科技专项资助（重大新药创新与发展）项目（No. 2018ZX09301053-004-001）；国家重点研究发展计划资助项目（No.2016YFC1200900）；长春市重大科技计划项目(No.16ss11)