Effect of hypoxia on human small cell lung cancer cell line H446
- VernacularTitle:缺氧对人小细胞肺癌细胞系H446细胞生物学特性的影响
- Publication Type:Journal Article
- Keywords: small cell lung cancer; hypoxia; drug-resistance; apoptotic potential cells; GRP78 stress
- From: China Oncology 2001;0(05):-
- CountryChina
- Language:Chinese
- Abstract: Background and purpose:Hypoxia has been clearly identifi ed as a physiological abnormality associated with solid tumors. Hypoxia can promote genetic instability, protect cancer cell from apoptosis, involve in treatment resistance, enhance metastatic potential and make cancer cells more aggressive. Those might be one of the major reasons accounting for higher malignancy and resistance to drugs in small cell lung cancer(SCLC). This study was to investigate the impact of the hypoxia effect on human small cell lung cancer cell line H446, and the signifi cance of the study not only is benefi cial to our understanding of this progress, but also to fi nd out new therapeutic targets. Methods:TEM, MTT and FACs were utilized to observe cellular morphological changes. The changes have been documented in terms of proliferation ability, medicine-sensitivity changes and the efficacy of drug exclusion and cell cycle of H446 cell line under the hypoxic condition, respectively. Meanwhile, luminometer, flow cytometry and fluorescence microscope were employed to detect the caspase-3/7 activity and generation of ROS, respectively. Furthermore, the expression of GRP78 at the mRNA level was measured by RT-PCR. Results:Under hypoxic condition, mitochondria swelling, organelle bubbling and myelinogenesis were obviously marked in some H446 cells, and microadencavity emerged in a few cells, but mellow damage was observed in most H446 cells. Meanwhile,the proliferation ability of H446 cell decreased signifi cantly, and H446 cells were less sensitive to mechlorethamine hydrochloride, VP-16 and doxorubicin (P