2017年第44卷第4期目录
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封面故事:肿瘤干细胞处于癌症细胞发展的金字塔顶端,与肿瘤的发展、抵抗化疗以及复发密切相关.溶瘤腺病毒作为靶向肿瘤细胞的新型基因治疗载体,已在临床上运用于多种恶性癌症的治疗.前期研究工作发现:携带TSLC1的溶瘤腺病毒对肝癌细胞具有良好的抑制作用.为了证明构建的溶瘤腺病毒对肿瘤干细胞的抑制效果,章健等以无血清悬浮培养富集肝癌干细胞作为测试对象,通过一系列实验检测溶瘤腺病毒对其抑制效果.封面中的图片清晰地呈现了贴壁生长的肝癌细胞到悬浮生长的肝癌干细胞的转变过程.封面中的荧光图片表明溶瘤腺病毒能有效抑制肝癌干细胞发生EMT转化.该论文的研究结果表明悬浮培养富集的球细胞具有肝癌干细胞特征,溶瘤腺病毒能有效抑制其迁移及侵袭,并靶向杀伤肝癌干细胞,显示其良好的临床应用前景.
(章 健,来维洁,李 强,金 槿,肖伯端,郭 婉,王毅刚.靶向Wnt信号的溶瘤腺病毒抑制肝癌干细胞研究,本期第326~337页)
Cover Story:Hepatocellular carcinoma (HCC) is the fifth largest cancer in the world and is the main cause of cancer death. Common treatment for early hepatocellular carcinoma has made some progress, but cancer recurrence, metastasis and drug resistance have not been fundamentally resolved, which can be explained by cancer stem cell theory (cancer stem cell, CSC). In this study, we obtained MHCC-97H sphere cells by suspension enrichment culture method and detected their stem cell characteristics. We deleted the 24 bp of the E1A CR2 region of the adenovirus type 5 and used the Wnt transcription element TCF/TEF to regulate E1A and then inserted the anti-oncogene TSLC1 into the vector to obtain the double targeting oncolytic adenovirus Ad.wnt-E1A(Δ24 bp)-TSLC1. The effect of recombinant adenovirus Ad.wnt-E1A(Δ24 bp)-TSLC1 on the killing effect, cell apoptosis and migration of hepatocarcinoma stem-like cells were detected by MTT, crystal violet, Hoechst staining, cell scratch, Western blot and immunofluorescence, respectively. The results show that MHCC-97H sphere cells have the capability of self-renewal and differentiation, and high expression of hepatocyte stem cell surface marker (such as CD133). After dealt with recombinant virus, it showed obvious killing effect and inhibition of cell migration and EMT (Epithelial-mesenchymal transition). Therefore, ability of targeting inhibition of 97H sphere cells was significantly higher than that of 97H cells (P<0.001). The recombinant virus could induce apoptosis of hepatocellular stem-like cells through caspase pathway. Therefore, the recombinant adenovirus Ad.wnt-E1A (Δ24 bp)- TSLC1 may be a promising therapeutic agent for targeting hepatoma stem cells, which has certain application value to clinical treatment.
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综述与专论
研究报告
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