کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5848222 | 1130145 | 2013 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells
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کلمات کلیدی
securinDIOC6PARPEGFRT-PCRPBSGFPFBSEGFRFITCDMSO - DMSOMTT - MTTGefitinib - جفیتینیب، ایرساApoptosis - خزان یاختهایPTTG - دبیرستانDimethyl sulfoxide - دیمتیل سولفواکسیدfetal bovine serum - سرم جنین گاوCancer cells - سلول های سرطانیepidermal growth factor - عامل رشد اپیدرمیfluorescein isothiocyanate - فلوئورسین ایسوتیوسیاناتPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریreverse transcription-polymerase chain reaction - واکنش زنجیره ای رونویسی-پلیمراز معکوسGreen fluorescence protein - پروتئین فلورسانس سبزPropidium iodide - پروتئین یدیدPoly(ADP-ribose) polymerase - پلیمر (ADP-ribose) پلیمرازEpidermal growth factor receptor - گیرنده فاکتور رشد اپیدرمال
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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چکیده انگلیسی
Gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), has been used to treat numerous cancers; however, evidence has shown that cancer cells can become resistant to gefitinib during therapy. Here, we report a human proto-oncogene, securin, which displays resistance to death in cancer cells. Gefitinib treatment decreases securin levels at the protein level by inducing protein instability but did not affect on the securin gene expression. Treatment with gefitinib induced cytotoxicity in various human cancer cell types, including RKO (colon cancer), A549 (lung cancer), BFTC905 (bladder cancer), MCF7 (breast cancer) and A375 (skin cancer). BFTC905 and A549 cells expressed relatively high levels of the phosphorylated and total EGFR proteins; however, A375, MCF7 and RKO cells did not markedly express these proteins. Moreover, following treatment with gefitinib, the securin-wild type cancer cells were more resistant to apoptotic induction than the securin-null cancer cells. Surprisingly, both the securin-wild type and securin-null cancer cells expressed the EGFR protein at similar levels. Treatment with gefitinib induced mitochondrial dysfunction, cytochrome c release, caspase-3 activation and poly (ADP-ribose) polymerase protein cleavage, indicating that apoptosis occurred in these cancer cells. The transfection of a GPF-securin expression vector increased both the proliferation rates and resistance to gefitinib-induced death in these cancer cells. Taken together, these findings demonstrate that the presence of securin promotes resistance to gefitinib-induced apoptosis via an EGFR-independent pathway in human cancer cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 203, Issue 2, 25 April 2013, Pages 412-422
Journal: Chemico-Biological Interactions - Volume 203, Issue 2, 25 April 2013, Pages 412-422
نویسندگان
Sheng-Yi Yu, Huei-Fang Liu, Su-Pei Wang, Chia-Ching Chang, Chuan-Mei Tsai, Jui-I Chao,