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.

[摘 要] 目的：探讨光甘草定对肺腺癌细胞A549恶性生物学行的影响及其分子机制。方法：常规方法培养A549细胞和人正常肺上皮细胞BEAS-2B，用不同浓度的光甘草定和或顺铂对其进行处理，通过结晶紫染色、CCK-8法检测光甘草定、顺铂对A549、BEAS-2B细胞增殖活力的影响，Transwell小室实验、细胞划痕实验检测光甘草定对A549细胞侵袭、迁移能力的影响，流式细胞术检测光甘草定对A549细胞凋亡的影响，3D超低黏附板培养法培养A549细胞后采用CCK-8法检测光甘草定对A549细胞增殖的影响，WB法检测光甘草定对A549细胞中上皮间质转化（EMT）相关蛋白表达的影响；构建A549细胞移植瘤模型后检测光甘草定、顺铂对移植瘤的生长以及移植瘤组织中EMT相关蛋白表达的影响。结果：光甘草定、顺铂呈剂量依赖性地显著抑制A549细胞的增殖（P<0.05或P<0.01）、细胞迁移（P<0.05或P<0.01）和侵袭能力（P<0.05或P<0.01），光甘草定能诱导A549细胞凋亡（P<0.01），抑制A549细胞中N-cadherin、snail和vimentin蛋白的表达，促进E-cadherin蛋白表达；光甘草定、顺铂均能抑制A549移植瘤的生长，抑制移植瘤组织中Ki67、N-cadherin、snail和vimentin蛋白的表达、促进E-cadherin蛋白的表达。结论：光甘草定可通过抑制A549细胞的增殖、迁移和侵袭，诱导A549细胞凋亡，其机制可能与其抑制细胞的EMT进程而产生抑癌作用有关。