Resistance to apoptosis induced by microenvironmental stresses is correlated with metastatic potential in Lewis lung carcinoma

Resistance to apoptosis induced by microenvironmental stresses is correlated with metastatic potential in Lewis lung carcinoma
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微环境应激诱导的细胞凋亡抵抗与Lewis肺癌的转移潜力相关

DOI:
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发表时间:
1999
影响因子:
4
通讯作者:
K. Takenaga
K. Takenaga
中科院分区:
医学3区
文献类型:
--
作者:
M. Takasu;Y. Tada;Jiyang Wang;M. Tagawa;K. Takenaga

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比较克隆的刘易斯肺癌高转移A11和低转移P29细胞的耐药表型。结果表明,A11细胞比P29细胞更能抵抗血清饥饿、葡萄糖剥夺和缺氧等微环境应激诱导的细胞凋亡。两种细胞系对肿瘤坏死因子-α介导的凋亡均不敏感。P29细胞表面Fas抗原表达水平明显高于A11细胞。然而,这两种细胞系也对Fas介导的凋亡不敏感。A11细胞的凋亡抵抗表型与caspase-3的表达水平有关,而与Bcl-2、Bcl-XL Bax、p27 Kip 1和DAP激酶的表达水平无关。A11和P29细胞在E-cadherin表达、对细胞外基质成分的粘附以及转移相关基因c-Ha-ras、c-jun、p53和nm 23的表达水平上均无差异。此外,A11细胞表现出较低的运动和侵袭能力比P29细胞。这些结果表明,抗肿瘤表型是决定A11细胞转移能力的重要因素。支持这一点,P29细胞在用二甲亚砜处理细胞后变得更具抗肿瘤性,据报道二甲亚砜增强了细胞的实验转移潜力。
The apoptosis-resistant phenotype of cloned high-metastatic A11 and low-metastatic P29 cells isolated from Lewis lung carcinoma was compared. The results showed that A11 cells were more resistant to apoptosis induced by microenvironmental stresses such as serum starvation, glucose deprivation and hypoxia than P29 cells as judged by viability, DNA laddering, and chromatin condensation and fragmentation. Both cell lines were insensitive to tumor necrosis factor-α-mediated apoptosis. P29 cells expressed a much higher level of Fas antigen on the cell surface than A11 cells. However, both cell lines were also insensitive to Fas-mediated apoptosis. The apoptosis resistant phenotype of A11 cells was associated with the expression level of caspase-3, but not with those of Bcl-2, Bcl-XL Bax, p27Kip1 and DAP kinase. There was no difference between A11 and P29 cells in the expression of E-cadherin, the adhesiveness to the extracellular matrix components or the expression levels of metastasis-associated genes such as c-Ha-ras, c-jun, p53 and nm23. Furthermore, A11 cells exhibited lower motile and invasive abilities than P29 cells. These results suggest that the apoptosis-resistant phenotype is an important factor for determining the metastatic ability of A11 cells. Supporting this, P29 cells became more apoptosis-resistant after treatment of the cells with dimethylsulfoxide which is reported to enhance the experimental metastatic potential of the cells.
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