Zheng Chenhong, Zhou Qi, Wu Feng, Peng Qiuping, Tang Airong, Liang Houjie, Zeng Yanjun
Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, China.
Chemotherapy. 2009;55(5):344-52. doi: 10.1159/000232449. Epub 2009 Aug 5.
Multicellular resistance (MCR), i.e. decreased sensitivity to anticancer drugs compared with common monolayer cell (MC) cultures, depends partly on tumor cell-cell adhesion. Previous studies have shown that anti-adhesive therapies, including integrin alpha(v), beta(1) and alpha(v)beta(3) targeting, induced apoptosis and reversed the sensitivity of MCR.
A model of three-dimensional cell culture was used to establish HT29 multicellular spheroid cells (MCS) and explore the effect of semaphorin3F (Sema3F) on integrin-mediated cell-cell interactions in MCS of a human colorectal adenocarcinoma cell line (HT29) and sensitization of HT29 MCS to 5-fluorouracil and oxaliplatin via a decrease in integrin alpha(v)beta(3).
Elevated expression of Sema3F led to the up-regulation neuropilin-2 (Nrp2) receptor expression and the down-regulation of integrin alpha(v)beta(3) expression. Furthermore, short interfering RNA of Nrp2 could reverse MCR.
Our study demonstrates that Sema3F can sensitize MCR by decreasing integrin alpha(v)beta(3)expression via the Nrp2 receptor.
多细胞耐药（MCR），即与普通单层细胞（MC）培养相比，对抗癌药物的敏感性降低，部分取决于肿瘤细胞间的黏附。先前的研究表明，包括靶向整合素α（v）、β（1）和α（v）β（3）的抗黏附疗法可诱导细胞凋亡并逆转MCR的敏感性。
使用三维细胞培养模型建立HT29多细胞球体细胞（MCS），并探讨信号素3F（Sema3F）对人结肠直肠腺癌细胞系（HT29）的MCS中整合素介导的细胞间相互作用的影响，以及通过降低整合素α（v）β（3）使HT29 MCS对5-氟尿嘧啶和奥沙利铂敏感。
Sema3F表达升高导致神经纤毛蛋白-2（Nrp2）受体表达上调和整合素α（v）β（3）表达下调。此外，Nrp2的短发夹RNA可逆转MCR。
我们的研究表明，Sema3F可通过Nrp2受体降低整合素α（v）β（3）的表达，从而使MCR敏感。
