Abstract：
:The mutation rates of tumor suppressor protein p53 gene (TP53) are high in lung adenocarcinoma and promote the development of acquired drug resistance. The present study evaluated the p53-dependent role in lung cancer cell sensitivity to PI3K-specific inhibitors, PI3K-associated inhibitors, PI3K-non-related inhibitors, and protein-based stimuli using designed p53 mutation. We found that the deletion of p53 key regions from amino acid 96 to 393 with the CRISPR-Cas9 altered multi-dimensional structure and sequencing of p53, probably leading the secondary changes in chemical structures and properties of PI3K subunit proteins or in interactions between p53 and PI3K isoform genes. The p53-dependent cell sensitivity varied among target specificities, drug chemical properties, mechanism-specific signal pathways, and drug efficacies, independently upon the size of molecules. The effects of the designed p53 mutation highly depend upon p53-involved molecular mechanisms in the cell. Our results indicate that lung cancer cell resistance to drug can develop with dynamic formations of p53 mutations changing the cell sensitivity. This may explain the real-time occurrence of cancer cell resistance to drug treatment, during which drugs may induce the new mutations of p53. Thus, it is important to dynamically monitor the formation of new mutations during the therapy and discover new drug resistance-specific targets.
journal_name
Cell Biol Toxicoljournal_title
Cell biology and toxicologyauthors
Hou J,Cao X,Cheng Y,Wang Xdoi
10.1007/s10565-020-09523-7subject
Has Abstractpub_date
2020-10-01 00:00:00pages
481-492issue
5eissn
0742-2091issn
1573-6822pii
10.1007/s10565-020-09523-7journal_volume
36pub_type
杂志文章abstract：:Cholestatic liver injury, a group of diseases characterized with dysregulated bile acid (BA) homeostasis, was partly resulted from BA circulation disorders, which is commonly associated with the damage of hepatocyte barrier function. However, the underlying hepatocyte barrier-protective molecular mechanisms of cholest...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-020-09567-9
更新日期：2021-01-05 00:00:00
abstract：:Oxidative cell injury could be induced by different reactive oxygen species (ROS) operating in multiple pathways. The present work is focused on three different models of oxidative stress: the xanthine/xanthine oxidase system (XXO), an extracellular superoxide anion generator; tert-butylhydroperoxide (TBHP), an analog...
journal_title：Cell biology and toxicology
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doi：10.1007/s10565-009-9120-3
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abstract：:Lung cancer is one of the most common malignancies worldwide. Actinidia chinensis Planch root extract (acRoots) was found to have the capacity of the anti-tumor, although the molecular mechanisms remain unclear. The present study aims to investigate the molecular mechanisms by which lung cancer cells sense to inhibito...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-018-9422-4
更新日期：2018-06-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-011-9200-z
更新日期：2012-02-01 00:00:00
abstract：:Although estrogens have been detected in some echinoderm species, their role is not clearly understood; so we examined the effects of estrogens administered to sea urchin embryos and larvae. A typical malformation was exogastrulation, induced by the exposure to ethynylestradiol (EER) in a defined period of 12 h from 1...
journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-008-9073-y
更新日期：2008-12-01 00:00:00
abstract：:The purpose of the study was to determine whether along and in combination melatonin (MLT) and pentoxifylline (PTX) exerted beneficial effects on histopathological changes and changes in oxidant and antioxidant systems in liver caused by CCl4-induced liver toxicity in mice. Mice were randomly divided into six groups: ...
journal_title：Cell biology and toxicology
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doi：10.1007/s10565-006-0019-y
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journal_title：Cell biology and toxicology
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doi：10.1007/s10565-013-9246-1
更新日期：2013-06-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1023/a:1020815723009
更新日期：2002-01-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章,评审
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更新日期：2007-07-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1023/a:1010907231602
更新日期：2001-01-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-020-09525-5
更新日期：2021-02-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-008-9061-2
更新日期：2008-12-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-007-9035-9
更新日期：2008-06-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00122655
更新日期：1989-06-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-006-0104-2
更新日期：2006-11-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-021-09580-6
更新日期：2021-01-23 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-010-9170-6
更新日期：2011-02-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-010-9175-1
更新日期：2011-04-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-013-9242-5
更新日期：2013-06-01 00:00:00
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doi：10.1007/s10565-008-9084-8
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00122694
更新日期：1986-06-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-008-9057-y
更新日期：2008-12-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-011-9186-6
更新日期：2011-08-01 00:00:00
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journal_title：Cell biology and toxicology
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doi：10.1023/a:1007606921569
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-013-9256-z
更新日期：2013-08-01 00:00:00
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pub_type： 杂志文章
doi：10.1007/s10565-010-9165-3
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00141285
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00124073
更新日期：1991-10-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/s10565-011-9201-y
更新日期：2012-02-01 00:00:00
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journal_title：Cell biology and toxicology
pub_type： 杂志文章
doi：10.1007/BF00438167
更新日期：1996-12-01 00:00:00
