Tong Xu-Hui, Dong Shu-Ying, Jiang Guo-Jun, Fan Gao-Fu
Department of Pharmacology, Faculty of Pharmacy, Bengbu Medical College, Bengbu, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2012 Mar;32(3):329-32.
To observe the influence of Cx26/Cx32 gap junction channel on the antineoplastic effect of etoposide in Hela cervical cancer cells.
Fluorescence trace was used to assay the gap junction intercellular communication mediated by Cx26/Cx32 in Hela cells and its functional modulation by the pharmacological agents (oleamide, retinoid acid). A standard colony-forming assay was applied to determine the cell growth-inhibiting effect of etoposide in Hela cells with functional modulation of the gap junction. Hoechst 33258 staining was used to assess the changes in etoposide-induced apoptosis of Hela cells with altered gap junction functions.
Oleamide markedly decreased while retinoid acid obviously increased the gap junction function in Hela cells. Standard colony-forming assay showed that etoposide produced a lowered antiproliferative effect in Hela cells with reduced gap junction and an increased antiproliferative effect in cells with enhanced gap junction function. In cells with a reduced gap junction function, etoposide induced a lowered apoptosis rate, which increased obviously in cells with an enhanced gap junction function.
The antineoplastic effect of etoposide is reduced in Hela cells with a decreased gap junction intercellular communication mediated by Cx26/Cx32 and is enhanced in cells with an increased gap junction intercellular communication.
观察Cx26/Cx32缝隙连接通道对依托泊苷在人宫颈癌Hela细胞中抗肿瘤作用的影响。
采用荧光示踪法检测Cx26/Cx32介导的Hela细胞缝隙连接细胞间通讯及其受药物(油酰胺、视黄酸)的功能调节。应用标准集落形成试验测定在缝隙连接功能受调节的情况下依托泊苷对Hela细胞的生长抑制作用。采用Hoechst 33258染色评估缝隙连接功能改变时依托泊苷诱导Hela细胞凋亡的变化。
油酰胺显著降低而视黄酸明显增强Hela细胞的缝隙连接功能。标准集落形成试验表明,在缝隙连接减少的Hela细胞中依托泊苷产生较低的抗增殖作用,而在缝隙连接功能增强的细胞中抗增殖作用增强。在缝隙连接功能降低的细胞中,依托泊苷诱导的凋亡率降低,而在缝隙连接功能增强的细胞中凋亡率明显升高。
在由Cx26/Cx32介导的缝隙连接细胞间通讯减少的Hela细胞中,依托泊苷的抗肿瘤作用降低;而在缝隙连接细胞间通讯增加的细胞中,其抗肿瘤作用增强。