Chen Shuang, Li Wenyao, Yin Xunzhe, Hu Cheng, Li Yiquan, Shao Xiaotong, Li Xiao, Jin Ningyi
School of Laboratory Medicine, Jilin Medical University, Jilin, China.
Institute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun, China.
Front Immunol. 2025 May 16;16:1530583. doi: 10.3389/fimmu.2025.1530583. eCollection 2025.
In this study, breast cancer cell line MCF-7 was infected with recombinant oncolytic adenovirus Ad-VT expressing apopsin protein, and its anti-tumour pathway was detected to determine its possible anti-tumour signalling pathway.
In this study, the inhibitory effect of recombinant oncolytic adenovirus Ad-VT on breast cancer cells was investigated through cell activity experiment and establishment of tumour bearing model in mice. Subsequently, in order to determine the apoptosis-inducing effect of recombinant oncolytic adenovirus on breast cancer cells, the effects of three recombinant oncolytic adenovirus on the apoptosis-inducing level of breast cancer cells were further analysed by Annexin V-FITC/PI detection, Hoechst staining, JC-1 staining and transmission electron microscopy. Then the differentially expressed proteins associated with apoptosis and possible signalling pathways were identified by proteomics and WB experiments.
and experiments showed that recombinant oncolytic adenovirus Ad-VT expressing apoptosis protein could induce apoptosis and inhibit the growth of MCF-7 cells. Proteomic analysis showed that differential genes were enriched in mTOR, MAPK and other pathways after Ad-VT infection of breast cancer cells, and the expression of S6K genes related to mTOR pathway was significantly increased in differential gene analysis, subsequently, the high expression of phosphorylated mTOR and S6K proteins was also determined by WB experiment, suggesting that Ad-VT may regulate the apoptosis of breast cancer cells through mTOR/S6K signalling.
Ad-VT can significantly increase the apoptosis level of breast cancer cells, which may be induced by the mTOR/S6K signalling pathway. The results of this study provide a theoretical basis for the development of anti-tumour drugs based on Ad-VT in the future.
本研究用表达凋亡素蛋白的重组溶瘤腺病毒Ad-VT感染乳腺癌细胞系MCF-7,检测其抗肿瘤途径,以确定其可能的抗肿瘤信号通路。
本研究通过细胞活性实验及建立小鼠荷瘤模型,研究重组溶瘤腺病毒Ad-VT对乳腺癌细胞的抑制作用。随后,为确定重组溶瘤腺病毒对乳腺癌细胞的诱导凋亡作用,通过Annexin V-FITC/PI检测、Hoechst染色、JC-1染色及透射电镜进一步分析三种重组溶瘤腺病毒对乳腺癌细胞诱导凋亡水平的影响。然后通过蛋白质组学和WB实验鉴定与凋亡相关的差异表达蛋白及可能的信号通路。
实验表明,表达凋亡蛋白的重组溶瘤腺病毒Ad-VT可诱导MCF-7细胞凋亡并抑制其生长。蛋白质组学分析显示,乳腺癌细胞经Ad-VT感染后,差异基因富集于mTOR、MAPK等通路,差异基因分析中与mTOR通路相关的S6K基因表达显著增加,随后WB实验也确定了磷酸化mTOR和S6K蛋白的高表达,提示Ad-VT可能通过mTOR/S6K信号通路调节乳腺癌细胞凋亡。
Ad-VT可显著提高乳腺癌细胞的凋亡水平,这可能由mTOR/S6K信号通路诱导。本研究结果为未来基于Ad-VT开发抗肿瘤药物提供了理论依据。