Improved Response by Co-targeting EGFR/EGFRvIII and Src Family Kinases in Human Cancer Cells

Andersen, Peter; Villingshøj, Mette; Poulsen, Hans Skovgaard; Stockhausen, Marie

doi:10.1080/07357900802570759

Cited by 11 publications

(9 citation statements)

References 21 publications

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“…Therefore, blocking phosphorylation of the site might have therapeutic benefits. AQP5 have been found expressed highly in primary human glioma cells compared with normal tissue, this is in accordance with the study that reported AQPs (such as AQP1 , AQP5 and AQP8 ) have been observed in high-grade tumors of various tissues [29, 30]. It is confirmed that high expression of AQP5 was associated with tumor growth, invasion and metastasis in non-small cell lung cancer [31].…”

Section: Discussionsupporting

confidence: 88%

Effects of AQP5 gene silencing on proliferation, migration and apoptosis of human glioma cells through regulating EGFR/ERK/ p38 MAPK signaling pathway

et al. 2017

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We investigated the effects of aquaporin 5 (AQP5) gene silencing on the proliferation, migration and apoptosis of human glioma cells through regulating the EGFR/ERK/p38MAPK signaling pathway. qRT-PCR was applied to examine the mRNA expressions of AQP5 in five human glioma cell lines. U87-MG, U251 and LN229 cells were selected and assigned into blank, vector, AQP5 siRNA and FlagAQP5 groups. MTT assay was used to measure cell proliferation. Flow cytometry (FCM) with AnnexinV-FITC/PI double staining and PI staining were employed to analyze cell apoptosis and cell cycle respectively. Scratch test was used to detect cell migration. Western blotting was performed to determine the EGFR/ERK/p38 MAPK signaling pathway-related proteins. Results showed that the positive expression of AQP5 in primary glioblastoma was associated with the tumor size and whether complete excision was performed. The mRNA expressions of AQP5 in cell lines of U87-MG, U251 and LN229 were significantly higher than in U373 and T98G. The proliferation rates of U87-MG, U251 and LN229 cells in the AQP5 siRNA group were lower than in the vector and blank groups. The apoptosis rate increased in the AQP5 siRNA group compared with the vector group. Scratch test demonstrated that AQP5 gene silencing could suppress cell migration. Compared with the vector and blank groups, the AQP5 siRNA group showed decreased expressions of the ERK1/2, p38 MAPK, p-ERK1/2 and p-p38 MAPK proteins. AQP5 gene silencing could inhibit the cell proliferation, reduce cell migration and promote the cell apoptosis of U87-MG, U251 and LN229 by suppressing EGFR/ERK/p38 MAPK signaling pathway.

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Section: Discussionsupporting

confidence: 88%

Effects of AQP5 gene silencing on proliferation, migration and apoptosis of human glioma cells through regulating EGFR/ERK/ p38 MAPK signaling pathway

et al. 2017

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“…2A and B). The enhanced effects of combined activation of targeting Src and EGFR signaling pathways are previously reported (6,20,(36)(37)(38). Furthermore, targeting Src in combination with trastuzumab-sensitized trastuzumabresistant cell lines (23), and inhibition of integrin/FAK/ Src pathway overcame lapatinib resistance (24).…”

Section: Discussionmentioning

confidence: 80%

Antitumor Activity of Saracatinib (AZD0530), a c-Src/Abl Kinase Inhibitor, Alone or in Combination with Chemotherapeutic Agents in Gastric Cancer

Nam

et al. 2013

Molecular Cancer Therapeutics

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Src is a nonreceptor tyrosine kinase involved in the cross-talk and mediation of many signaling pathways that promote cell proliferation, adhesion, invasion, migration, and tumorigenesis. Increased Src activity has been reported in many types of human cancer, including gastric cancer. Therefore, this factor has been identified as a promising therapeutic target for cancer treatments, and targeting Src in gastric cancer is predicted to have potent effects. We evaluated the antitumor effect of a c-Src/Abl kinase inhibitor, saracatinib (AZD0530), alone or combined with chemotherapeutic agents in gastric cancer cell lines and a NCI-N87 xenograft model. Among 10 gastric cancer cell lines, saracatinib specifically inhibited the growth and migration/invasion of SNU216 and NCI-N87 cells. Saracatinib blocked the Src/FAK, HER family, and oncogenic signaling pathways, and it induced G 1 arrest and apoptosis in SNU216 and NCI-N87 cells. Apoptosis required induction of the proapoptotic BCL2 family member Bim. Knockdown of Bim using siRNA decreased apoptosis induced by treatment with saracatinib, suggesting that Bim has an important role in saracatinibinduced apoptosis. Saracatinib enhanced the effects of lapatinib, an EGFR/HER2 dual inhibitor, in SNU216 and NCI-N87 cells. Furthermore, combined treatment with saracatinib and 5-fluorouracil (5-FU) or cisplatin exerted synergistic effects in both saracatinib-sensitive and saracatinib-resistant cells. Consistent with our in vitro findings, cotreatment with saracatinib and 5-FU resulted in enhanced antitumor activity in the NCI-N87 xenografts. These data indicate that the inhibition of Src kinase activity by saracatinib alone or in combination with other agents can be a strategy to target gastric cancer.

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“…44 Decreased c-Src kinase activity resulted in increased sensitivity to EGFR inhibitors in head and neck cancer and epidermoid carcinoma cell lines. 45,46 A recent Phase I/II study has also been published utilizing dasatinib in combination with the EGFR TKI erlotinib in non-small cell lung cancer. 47 Not only was this combination tolerable in patients, but disease control was also observed.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Src family kinases mediate epidermal growth factor receptor signaling from lipid rafts in breast cancer cells

Irwin

Bohin

Boerner

2011

Cancer Biology & Therapy

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Improved Response by Co-targeting EGFR/EGFRvIII and Src Family Kinases in Human Cancer Cells

Cited by 11 publications

References 21 publications

Effects of AQP5 gene silencing on proliferation, migration and apoptosis of human glioma cells through regulating EGFR/ERK/ p38 MAPK signaling pathway

Effects of AQP5 gene silencing on proliferation, migration and apoptosis of human glioma cells through regulating EGFR/ERK/ p38 MAPK signaling pathway

Antitumor Activity of Saracatinib (AZD0530), a c-Src/Abl Kinase Inhibitor, Alone or in Combination with Chemotherapeutic Agents in Gastric Cancer

Src family kinases mediate epidermal growth factor receptor signaling from lipid rafts in breast cancer cells

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