Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
Int J Oncol. 2012 Jan;40(1):109-18. doi: 10.3892/ijo.2011.1181. Epub 2011 Aug 31.
Mitochondrial DNA-depleted ρ0 cells are resistant to apoptosis, but the mechanism remains unclear. A human hepatoma cell line (SK-Hep1) depleted of mtDNA (ρ0SK-Hep1) was induced by ethidium bromide treatment. The ρ0SK-Hep1 cells were resistant to both doxorubicin- and cisplatin-induced apoptosis, while cybrids (SK-Hep1Cyb) prepared by fusing ρ0SK-Hep1 cells with platelets showed restored susceptibility to both drugs. We observed P-glycoprotein and MRP1 were both overexpressed in ρ0 cells, and more P-glycoproteins were localized in the mitochondria and were functionally active. ρ0 cells showed resistance to chemotherapeutic drug-induced apoptosis. The increased expression and localization of P-glycoproteins in the mitochondria of ρ0 cells may facilitate the exclusion of chemotherapeutic drugs from the mitochondria to the cytosol.
ρ0 细胞缺失线粒体 DNA 后对细胞凋亡有抗性，但具体机制尚不清楚。我们通过溴化乙锭处理诱导人肝癌细胞系（SK-Hep1）缺失线粒体 DNA（ρ0SK-Hep1）。结果显示，ρ0SK-Hep1 细胞对阿霉素和顺铂诱导的细胞凋亡均有抗性，而将 ρ0SK-Hep1 细胞与血小板融合制备的细胞杂交体（SK-Hep1Cyb）对这两种药物的敏感性均恢复。我们观察到 ρ0 细胞中 P-糖蛋白和多药耐药相关蛋白 1（MRP1）均过度表达，并且更多的 P-糖蛋白定位于线粒体中且具有功能活性。ρ0 细胞对化疗药物诱导的细胞凋亡有抗性。ρ0 细胞中线粒体中 P-糖蛋白表达和定位的增加可能有助于将化疗药物从线粒体排出到细胞质中。
