He Jian-Ming, Wang Feng-Chao, Qi Hua-Bing, Li Yan, Liang Hou-Jie
Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Cancer Lett. 2009 Nov 1;284(2):182-8. doi: 10.1016/j.canlet.2009.04.023. Epub 2009 May 10.
Since multicellular resistance (MCR) has been shown to be as adhesion-dependent, the role of alphav integrin in MCR of HT29 was investigated in this paper. Down-regulation of alphav integrin reduced MCR to oxaliplatin, but did not detectably change the drug sensitivity of monolayers. Down-regulation of alphav integrin decreased phosphorylated NF-kappaB p65 and increased phosphorylated JNK2 in multicellular spheroids. Cell-cell adhesion and cell-cell junctions in multicellular spheroids resembled the in vivo situation. Since force, including adhesion, can activate alphav integrin, cell-cell contact may contribute to activation of alphav integrin, through which increasing phosphorylated p65 and decreasing phosphorylated JNK2 takes part in MCR.
由于多细胞耐药性（MCR）已被证明与黏附相关，本文研究了αv整合素在HT29细胞MCR中的作用。αv整合素的下调降低了对奥沙利铂的MCR，但未显著改变单层细胞的药物敏感性。αv整合素的下调降低了多细胞球体中磷酸化的NF-κB p65水平，并增加了磷酸化的JNK2水平。多细胞球体中的细胞间黏附和细胞间连接类似于体内情况。由于包括黏附在内的力可以激活αv整合素，细胞间接触可能有助于αv整合素的激活，通过这种方式，增加磷酸化的p65并降低磷酸化的JNK2参与MCR。
