FAK alleviates radiation-induced rectal injury by decreasing apoptosis

Li, Jun; Tu, Wenzhi; Chen, Xuming; Hu, Yutong; Chen, Ying; Ge, Yulong; Wang, Jing; Xu, Yi; Chen, Tingfeng; Zhang, Xiaowei; Ye, Jin-Jun; Liu, Yong

doi:10.1016/j.taap.2018.10.007

Cited by 4 publications

(2 citation statements)

References 49 publications

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“…Previous research has exhibited that a downstream molecule of the integrin receptor FAK, suppresses apoptosis by activating the downstream effector Akt (25,26). FAK alleviates radiation-induced rectal injury by decreasing apoptosis (27). Interestingly, FAK activation may facilitate tumour initiation by causing resistance to apoptosis (28).…”

Section: Discussionmentioning

confidence: 99%

Artesunate alleviates myocardial ischemia/reperfusion-induced myocardial necrosis in rats and hypoxia/reoxygenation-induced apoptosis in H9C2 cells via regulating the FAK/PI3K/Akt pathway

Fan¹,

Zhang²,

Liu³

et al. 2020

Ann Transl Med

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Background: The various anti-inflammatory, anti-apoptotic, and antioxidant effects of Artesunate (Art) have been explored in numerous studies. This study aimed to evaluate the function of Art on myocardial necrosis in apoptotic cardiomyocytes in vivo and in vitro.Methods: Sprague Dawley (SD) rats were randomly divided into groups: a control group, a myocardial ischemia reperfusion (MI/R) group, and MI/R+ Art groups. To establish a MI/R model, rats were subjected to left anterior descending artery ischemia for 45 minutes, and then reperfusion for 2 hours. Hypoxia was induced in H9C2 cells by subjecting them to hypoxic conditions at 37 ℃ for 4 hours, before placing them in a normoxic chamber for 2 hours. The test methods were used in this test, such as echocardiography, enzyme-linked immunosorbent assay (ELISA), HE staining, TUNEL staining, immunohistochemistry, flow cytometry, western blot, and CCK-8 assay. Results: Art improved myocardial systolic function caused by MI/R injury in vivo. Simultaneously, Art reduced the levels of cardiac troponin I (cTnl), creatine kinase-MB (CK-MB) and myohemoglobin (Mb) in vivo and in vitro. Moreover, Art inhibited cardiomyocyte apoptosis in vivo and in vitro. The focal adhesion kinase (FAK)/phosphatidylinositide-3 kinases (PI3K)/AKT signaling pathway was also activated by Art in vivo and in vitro. Furthermore, after inhibitor PF573228 was added, Art inhibited apoptosis in H9C2 cells via activation of the FAK/PI3K/AKT signaling pathway in vitro.Conclusions: This study confirms that Art alleviated MI/R injury and inhibited cardiomyocyte apoptosis in vivo and in vitro. Art exerted an inhibitory effect on cardiomyocyte apoptosis by activating the FAK/PI3K/ AKT signaling pathway. Therefore, Art may serve as an alternative treatment for MI/R injury.

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Section: Discussionmentioning

confidence: 99%

Artesunate alleviates myocardial ischemia/reperfusion-induced myocardial necrosis in rats and hypoxia/reoxygenation-induced apoptosis in H9C2 cells via regulating the FAK/PI3K/Akt pathway

Fan¹,

Zhang²,

Liu³

et al. 2020

Ann Transl Med

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“…A recent study identified that Fak may mediate the radioresistance of HIEC cells. Fak knockdown markedly increased the radiosensitivity of HIEC cells, and mice treated with FAK inhibitors exhibited aggravated mice rectal damage (31). In addition, Zhang et al (32) identified that β1-integrin-blocking antibody and FAK inhibitor-enhanced radiation induced apoptosis in esophageal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Association between breast cancer cell migration and radiosensitivity in�vitro

Hou

Zhu

et al. 2019

Oncol Lett

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The aim of the present study was to examine the association between the migration of breast cancer cells in vitro and radiosensitivity by establishing a breast cancer cell model with different migratory capacities. Transwell chambers in a 24-well plate were used to separate MDA-MB-231 and ZR-7530 cells and to establish cell models with different migratory capacities. Subsequently, the radiosensitivity of the cell models was measured using a radiation clone formation assay. Furthermore, differential gene expression was determined using gene microarray analysis. The protein expression levels of the differentially expressed genes (DEGs) were assessed using western blot analysis. From each parental cell line, a pair of daughter cell lines were established in with differing migratory abilities. These daughter cell lines were named MDA-MB-231 UP-10 (231 UP-10), MDA-MB-231 Down-10 (231 Down-10), ZR-75-30 UP-10 (7530 UP-10) and ZR-75-30 Down-10 (7530 Down-10). Radiation clone formation assays revealed that the cell lines with increased migratory abilities (231 Down-10 and 7530 Down-10) demonstrated higher radio-resistance compared with the cell lines with decreased migratory abilities (231 UP-10 and 7530 UP-10). Gene microarrays identified numerous DEGs between the pairs of UP and Down cell lines. A focus was placed on genes associated with cell adhesion and it was identified that phosphorylated Fak and phosphorylated EGFR expression levels were increased in 231 Down-10 and 7530 Down-10 cells, compared with the 231 UP-10 and 7530 UP-10 cells. Other genes including ZO-1, FN1 and SOX9 expression were also increased in the 231 Down-10 and 7530 Down-10 cells compared with 231 UP-10 and 7530 UP-10 cells. Cell lines with increased migratory capacities may be more radio-resistant compared with cell lines with a decreased migratory capabilities. The mechanism may be associated with changes in the expression of cell adhesion molecules and epithelial-mesenchymal transition (EMT). Therapeutic strategies targeting cell adhesion or EMT may increase the radiation sensitivity of breast cancer cells, in addition to improving the effect of radiation therapy.

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Proteomic analysis of acute radiation-induced rectal injury in rats

Zhu,

Dai,

et al. 2023

Radiation Medicine and Protection

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FAK alleviates radiation-induced rectal injury by decreasing apoptosis

Cited by 4 publications

References 49 publications

Artesunate alleviates myocardial ischemia/reperfusion-induced myocardial necrosis in rats and hypoxia/reoxygenation-induced apoptosis in H9C2 cells via regulating the FAK/PI3K/Akt pathway

Artesunate alleviates myocardial ischemia/reperfusion-induced myocardial necrosis in rats and hypoxia/reoxygenation-induced apoptosis in H9C2 cells via regulating the FAK/PI3K/Akt pathway

Association between breast cancer cell migration and radiosensitivity in�vitro

Proteomic analysis of acute radiation-induced rectal injury in rats

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