کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5506014 | 1400283 | 2017 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Modulation of the sphingolipid rheostat is involved in paclitaxel resistance of the human prostate cancer cell line PC3-PR
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کلمات کلیدی
nSMaseTSAqRT-PCRSPLSphK1PDMPPTXS1PPPMPSMaseDNRGCsASMaseLC-MS/MS - LC-MS / MSacid sphingomyelinase - اسفنجی مینولیز اسیدSphingosine 1-phosphate lyase - اسپینوزین 1 فسفات لیائازsphingosine 1-phosphate - اسپینگزین 1-فسفاتsphingomyelinase - اسپینگومایینازneutral sphingomyelinase - اسپینگومییلیناز خنثیacid ceramidase - اسید سرامیدازTrichostatin A - تریکوستاتین ADaunorubicin - داونوروبیسینhuman prostate cancer cell line - سلول سرطانی سرطان پروستات انسانPaclitaxel resistance - مقاومت پکلیتاکسلquantitative reverse transcription polymerase chain reaction - واکنش زنجیره ای پلی مراز رونویسی معکوسPaclitaxel - پاکلی تاکسلliquid chromatography–tandem mass spectrometry - کروماتوگرافی مایع و اسپکترومتری توده دو طرفهglucosylceramide synthase - گلوکوزیلسرامید سنتاز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Taxoids are anti-cancer drugs frequently used to treat solid tumors, but they are sometimes ineffective and tumors may become resistant to their action. Here, we examined the involvement of sphingolipid metabolic enzymes in paclitaxel (PTX) resistance using a human prostate cancer cell line, PC3, and its PTX-resistant subline, PC3-PR. PTX (20Â nM) suppressed cell proliferation and increased various ceramide species in PC3, but not PC3-PR, cells. PC3-PR contained higher S1P levels than did PC3, regardless of PTX treatment. Western blotting revealed that PC3-PR cells expressed higher levels of sphingosine kinase 1 (SPHK1) and glucosylceramide synthase (GCS) but lower levels of acid sphingomyelinase (ASMase) and neutral sphingomyelinase 2 than did PC3 cells. Inhibition of SPHK1 using siRNA or a pharmacological inhibitor decreased S1P levels in PC3-PR cells and inhibited proliferation in the presence or absence of PTX, suggesting that SPHK1 is at least partially responsible for PTX resistance. Similarly, GCS inhibitors (PDMP and PPMP) increased cellular ceramides and suppressed the proliferation of PC3-PR. However, inhibition of proteasome function or histone deacetylase activity increased SMase and ceramide levels and suppressed PC3-PR proliferation. These results suggest that modulation of metabolic enzyme expression and alteration of the sphingolipid rheostat protects cancer cells against PTX.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 486, Issue 2, 29 April 2017, Pages 551-557
Journal: Biochemical and Biophysical Research Communications - Volume 486, Issue 2, 29 April 2017, Pages 551-557
نویسندگان
Yuka Aoyama, Sayaka Sobue, Naoki Mizutani, Chisato Inoue, Yoshiyuki Kawamoto, Yuji Nishizawa, Masatoshi Ichihara, Mamoru Kyogashima, Motoshi Suzuki, Yoshinoti Nozawa, Takashi Murate,