CCK-8. Western blot 78 glucose regulated protein 78 GRP78 C /EBP. C /EBP homologous protein CHOP. poly ADP-ribose polymerase PARP

Σχετικά έγγραφα
Μελέτη της έκφρασης του ογκοκατασταλτικού γονιδίου Cyld στον καρκίνο του μαστού

B16F10 SDS-PAGE. Annexin V-FITC /PI

ΜΟΡΙΑΚΕΣ ΜΕΘΟΔΟΙ ΚΡΙΤΗΡΙΑ ΕΠΙΛΟΓΗΣ ΑΞΙΟΛΟΓΗΣΗ

CPT. Tsuchiya. beta. quantitative RT PCR QIAGEN IGFBP. Fect Transfection Reagent sirna. RT PCR RNA Affymetrix GeneChip Expression Array

IL - 13 /IL - 18 ELISA PCR RT - PCR. IL - 13 IL - 18 mrna. 13 IL - 18 mrna IL - 13 /IL Th1 /Th2

http / /cjbmb. bjmu. edu. cn Chinese Journal of Biochemistry and Molecular Biology GLC-82 GRP78 CHOP

ACTA CHINESE MEDICINE. diabetic nephropathies DN 24. urine protein quantitation in 24 hours 24hUTP serum creatinine Scr

ACTA UN IVER SITATIS TR ADITIO N IS M EDICALIS SIN EN SIS PHAR M ACO LO GIAEQ UE SHAN GHAI Vol. 29 N o. 3 M ay 2015

Journal of Ningxia Medical University. Annexin P19 mrna P < AnnexinA2 P19 mrna. AnnexinA2 P19 mrna. PCR 1.

HepG hotmail. com. HepG2 Bid Bcl-2. HepG2 G0 /G1 Bid Bcl-2. HepG2. HepG2

BGP TRACP-5b BGP TRACP-5b P 0.05

PE CVVH PE+HP HP+CVVH HP+CVVH+PE CVVH. ENLAV of HCO - 3 ENLAV-HCO ± μmol /L HP+PE HP+CVVH HP+CVVH+PE

Journal of Experimental Hematology * AA005. AA005 > 200 nmol /L AA005 NB4 U937 K h R R A

A X All-trans retinoic acid ATRA LS174T

KLT SMMC Anti - tumor effect in vitro of coix seed oil injection on the human liver cancer cell SMMC and the mechanism study

Supporting Information

ΠΡΟΓΡΑΜΜΑ ΜΕΤΑΠΤΥΧΙΑΚΩΝ ΣΠΟΥΔΩΝ ΣΤΙΣ «ΚΛΙΝΙΚΕΣ ΚΑΙ ΚΛΙΝΙΚΟΕΡΓΑΣΤΗΡΙΑΚΕΣ ΙΑΤΡΙΚΕΣ ΕΙΔΙΚΟΤΗΤΕΣ»

ΣΤΡΩΜΑΤΙΚΟΙ ΟΓΚΟΙ ΓΑΣΤΡΕΝΤΕΡΙΚΟΥ ΣΥΣΤΗΜΑΤΟΣ (GISTs) ΕΛΕΝΗ ΠΑΠΑΔΑΚΗ ΠΑΘΟΛΟΓΟΑΝΑΤΟΜΟΣ ΝΟΣΟΚΟΜΕΙΟ ΠΑΤΡΩΝ «ΑΓΙΟΣ ΑΝΔΡΕΑΣ»

Basic & Clinical Medicine PLGA MUC1 MUC1 IC 50 MUC1 +

Development of the Nursing Program for Rehabilitation of Woman Diagnosed with Breast Cancer

Octretide joint proton pump inhibitors in treating non-variceal gastrointestinal bleeding a Metaanalysis

Εθνικό Μετσόβιο Πολυτεχνείο ΑΝΑΠΤΥΞΗ ΤΕΧΝΙΚΗΣ ΜΕΤΡΗΣΗΣ ΕΚΚΡΙΣΗΣ ΠΡΩΤΕΪΝΩΝ ΚΟΝΤΑ ΣΤΗ ΚΥΤΤΑΡΙΚΗ ΕΠΙΦΑΝΕΙΑ

HIV HIV HIV HIV AIDS 3 :.1 /-,**1 +332

Endoplasmic Reticulum Stress and Mammalian Male Reproduction

Science of Sericulture

A Systematic Review of Procalcitonin for Early Detection of Septicemia of Newborn

Βιοδείκτες οξειδωτικού στρες

http / / cjbmb. bjmu. edu. cn Chinese Journal of Biochemistry and Molecular Biology HBx HBxΔ127

Accumulation of Soil Arsenic by Panax notoginseng and Its Associated Health Risk

Inhibition of mushroom tyrosinase by flavonoid from Sorbus tianschanica Ruper in Xinjiang

Optimizing Microwave-assisted Extraction Process for Paprika Red Pigments Using Response Surface Methodology

The signal transduction of unfolded protein response

Comparison of carbon-sulfur and carbon-amine bond in therapeutic drug: -S-aromatic heterocyclic podophyllum derivatives display antitumor activity

MSM Men who have Sex with Men HIV -

Gro wth Properties of Typical Water Bloom Algae in Reclaimed Water

Supporting Information

0. 35g kg ~ 2. 0cm 10min. Nar- 15μL 6mm

Reaction of a Platinum Electrode for the Measurement of Redox Potential of Paddy Soil

Effects of soothing liver and invigorating spleen recipes of TCM on hepatic inflammatory cytokines of rats with nonalcoholic steatosishepatitis

The toxicity of three chitin synthesis inhibitors to Calliptamus italicus Othoptera Acridoidea

ΤΕΧΝΟΛΟΓΙΚΟ ΕΚΠΑΙ ΕΥΤΙΚΟ Ι ΡΥΜΑ ΚΡΗΤΗΣ ΣΧΟΛΗ ΙΟΙΚΗΣΗΣ ΚΑΙ ΟΙΚΟΝΟΜΙΑΣ ΤΜΗΜΑ ΙΟΙΚΗΣΗΣ ΕΠΙΧΕΙΡΗΣΕΩΝ ΠΤΥΧΙΑΚΗ ΕΡΓΑΣΙΑ

ΤΕΧΝΟΛΟΓΙΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΚΥΠΡΟΥ ΤΜΗΜΑ ΝΟΣΗΛΕΥΤΙΚΗΣ

Contents Part I Psychoneuroimmunology and Systems Biology Mechanisms 1 From Psychoneuroimmunology to Personalized, Systems, and Dynamical Medicine

ΤΕΧΝΟΛΟΓΙΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΚΥΠΡΟΥ ΣΧΟΛΗ ΕΠΙΣΤΗΜΩΝ ΥΓΕΙΑΣ ΤΜΗΜΑ ΝΟΣΗΛΕΥΤΙΚΗΣ ΠΤΥΧΙΑΚΗ ΕΡΓΑΣΙΑ ΕΠΗΡΕΑΖΕΙ ΤΗΝ ΠΡΟΛΗΨΗ ΚΑΡΚΙΝΟΥ ΤΟΥ ΜΑΣΤΟΥ

Παιδιατρική ΒΟΡΕΙΟΥ ΕΛΛΑΔΟΣ, 23, 3. Γ Παιδιατρική Κλινική, Αριστοτέλειο Πανεπιστήμιο, Ιπποκράτειο Νοσοκομείο Θεσσαλονίκης, 2

ΙΩΑΝΝΗΣ ΚΛΑΓΚΑΣ. Χημικός, MSc ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ ΥΠΟΒΛΗΘΗΚΕ ΣΤΗΝ ΙΑΤΡΙΚΗ ΣΧΟΛΗ ΤΟΥ ΑΡΙΣΤΟΤΕΛΕΙΟΥ ΠΑΝΕΠΙΣΤΗΜΙΟΥ ΘΕΣΣΑΛΟΝΙΚΗΣ

Survivin sirna. Inhibitory effect of small interference RNA targeting survivin nanospheres on human pancreatic carcinoma BXPC-3 cell growth

Chinese Journal of Biochemistry and Molecular Biology. p38mapk

Supporting Information. Asymmetric Binary-acid Catalysis with Chiral. Phosphoric Acid and MgF 2 : Catalytic

Cinnamaldehyde Prevents Endothelial Dysfunction Induced by High Glucose by Activating Nrf2

Extract Isolation Purification and Identification of Polysaccharides from Exocarp of Unripe Fruits of Juglans mandshurica

Αθήνα, 15 Οκτωβρίου 2014 Αρ. Πρωτ.: 2988

ΑΡΙΣΤΟΤΕΛΕΙΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΘΕΣΣΑΛΟΝΙΚΗΣ ΙΑΤΡΙΚΗ ΣΧΟΛΗ. ΠΡΟΓΡΑΜΜΑ ΜΕΤΑΠΤΥΧΙΑΚΩΝ ΣΠΟΥ ΩΝ «Ιατρική Ερευνητική Μεθοδολογία» ΙΠΛΩΜΑΤΙΚΗ ΕΡΓΑΣΙΑ

ER PR ~ 81. Estrogen Receptor ER 50 ± D5 1A6 CB11 STOVT3D1 EliVision 1. 3.

Effect of shengjiang powder on protection of myocardial injury in patients with sepsis

High mobility group 1 HMG1

Ankylosing Spondylitis AS. NSAIDs. NSAIDs 100% B27 NSAID ~ 90% FDA EMA

ER-Tree (Extended R*-Tree)

Βιταμίνη D και καρκίνος

Cellular Physiology and Biochemistry

ΜΕΤΑΠΤΥΧΙΑΚΗ ΕΡΕΥΝΗΤΙΚΗ ΔΙΑΤΡΙΒΗ

Relationship between Connective Tissue Diseases and Thyroid Diseases

Gerard A. Silvestri, MD, FCCP; and M. Patricia Rivera, MD, FCCP NSCLC EGFR NSCLC EGFR EGFR NSCLC. (epidermal growth factor receptor);

Αξιολόγηση των εκπαιδευτικών δραστηριοτήτων των νοσοκομειακών βιβλιοθηκών.

ΤΕΧΝΟΛΟΓΙΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΚΥΠΡΟΥ ΣΧΟΛΗ ΕΠΙΣΤΗΜΩΝ ΥΓΕΙΑΣ

Biapenem BIPM Lot No g mg

Antimicrobial Ability of Limonene, a Natural and Active Monoterpene

BD Cytometric Bead Array Flex Set System

Πτυχιακή Εργασία Η ΠΟΙΟΤΗΤΑ ΖΩΗΣ ΤΩΝ ΑΣΘΕΝΩΝ ΜΕ ΣΤΗΘΑΓΧΗ

Μελέτη της επίδρασης αντικαρκινικών χημειοθεραπευτικών φαρμάκων στη ρύθμιση του Cdt1

Apoptosis Induced by Glucose-6-phosphate Dehydrogenase Deficiency is Mediated by Caspase-3 and PARP-1 in Human Melanoma Cells

υγεία των νοσηλευτών που συστηματικά εμπλέκονται στην παρασκευή και χορήγηση τους.

ΔΙΕΡΕΥΝΗΣΗ ΤΗΣ ΣΕΞΟΥΑΛΙΚΗΣ ΔΡΑΣΤΗΡΙΟΤΗΤΑΣ ΤΩΝ ΓΥΝΑΙΚΩΝ ΚΑΤΑ ΤΗ ΔΙΑΡΚΕΙΑ ΤΗΣ ΕΓΚΥΜΟΣΥΝΗΣ ΤΕΧΝΟΛΟΓΙΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΚΥΠΡΟΥ ΣΧΟΛΗ ΕΠΙΣΤΗΜΩΝ ΥΓΕΙΑΣ

thrombolysis in myocardial infarction TIMI 5 /6 vs 3 /13 P < /30 vs 15 /30 P < 0.

Κυτταρική Επικοινωνία Cell Communication

ΤΕΧΝΟΛΟΓΙΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΚΥΠΡΟΥ ΣΧΟΛΗ ΕΠΙΣΤΗΜΩΝ ΥΓΕΙΑΣ. Πτυχιακή διατριβή. Ονοματεπώνυμο: Αργυρώ Ιωάννου. Επιβλέπων καθηγητής: Δρ. Αντρέας Χαραλάμπους

Experimental Study of Dielectric Properties on Human Lung Tissue

Comparison of HPLC fingerprint between enzymatic Calculus bovis and natural Calculus bovis

Χρηµατοδότηση: Ε.Ε., ΚΕΟΣΟΕ (Γ.Γ.Ε.Τ. ΠΕΝΕΔ 2001)

Electrolyzed-Reduced Water as Artificial Hot Spring Water

Mitomycin C application for the prevention of postoperative synechiae formation at the anterior commissure.

1 h, , CaCl 2. pelamis) 58.1%, (Headspace solid -phase microextraction and gas chromatography -mass spectrometry,hs -SPME - Vol. 15 No.

Abstract... I. Zusammenfassung... II. 1 Aim of the work Introduction Short overview of Chinese hamster ovary cell lines...

Mouse Gene 2.0 ST Array Shn3. Runx2 Shn3. Runx2 Shn3 Runx2. adult. (Schnurri, Shn)3/Hivep3. Runx2 Shn/Hivep. ST2 BMP-2 Shn3

Studies on the Binding Mechanism of Several Antibiotics and Human Serum Albumin

Research on Economics and Management

Παρουσίαση περιστατικού: Φαρμακευτική πολυπεκτομή με μακροχρόνια λήψη μοντελουκάστης.

α 1 2- Cloning and Expression of alpha 1 2-fucosyltransferase in E. coli BIOTECHNOLOGY BULLETIN

þÿ ɺÁ Ä ÅÂ, ±»Î¼ Neapolis University þÿ Á̳Á±¼¼± ¼Ìù±Â ¹ º à Â, Ç» Ÿ¹º ½ ¼¹ºÎ½ À¹ÃÄ ¼Î½ º±¹ ¹ º à  þÿ ±½µÀ¹ÃÄ ¼¹ µ À»¹Â Æ Å

Monday 26 January2015

Η ΦΛΕΓΜΟΝΩ ΗΣ ΑΝΤΙ ΡΑΣΗ ΤΟΥ ΓΑΣΤΡΙΚΟΥ ΒΛΕΝΝΟΓΟΝΟΥ ΣΤΗ ΛΟΙΜΩΞΗ ΜΕ ΕΛΙΚΟΒΑΚΤΗΡΙ ΙΟ ΤΟΥ ΠΥΛΩΡΟΥ ΠΡΙΝ ΚΑΙ ΜΕΤΑ ΤΗ ΘΕΡΑΠΕΙΑ

The influence of various blood purification methods on intradialytic hypotension in maintenance dialysis

Antitumor effect of Xiaojin Capsules on xenotransplanted tumor in zebrafish

Οι επιδόσεις Ελλήνων στο Mini Mental State Examination με βάση την ηλικία και τη νοητική κατάσταση από την παιδική στην τρίτη ηλικία.

ΕΦΑΡΜΟΓΗ ΕΥΤΕΡΟΒΑΘΜΙΑ ΕΠΕΞΕΡΓΑΣΜΕΝΩΝ ΥΓΡΩΝ ΑΠΟΒΛΗΤΩΝ ΣΕ ΦΥΣΙΚΑ ΣΥΣΤΗΜΑΤΑ ΚΛΙΝΗΣ ΚΑΛΑΜΙΩΝ

Chapter 1. Fingolimod attenuates ceramide induced blood-brain barrier dysfunction in multiple sclerosis by targeting reactive astrocytes

Preparation and identification of adr 5 ScFv loaded GCS and assaying its antitumor

BD OptEIA ELISA Sets ELISA

17 min R A (2009) To probe into the thermal property the mechanism of the thermal decomposition and the prospective

Ποιοτική Αξιολόγηση ενός Προγράμματος Διδασκαλίας Δεξιοτήτων Ζωής στη Φυσική Αγωγή

Transcript:

2016 31 1 29 DMAS PERK NSCLC PC9 /GR 1 2* 3 1. 310053 2. 310006 3. 310006 β β'- β dimethylacryl shikonin DMAS PKR ER PKR-like ER kinaseperk PC9 /GR DMAS PC9 /GR CCK-8 Western blot 78 glucose regulated protein 78 GRP78 C /EBP C /EBP homologous protein CHOP unfolded protein response UPR PERK GSK2606414 Annexin-V-PI Western blot caspase-3 caspase-8 caspase-9 poly ADP-ribose polymerase PARP DMAS 0 5 10 15 μmol /L PC9 /GR P < 0. 05 DMAS PC9 /GR caspase-3 caspase-8 caspase-9 PARP P < 0. 05 GRP78 CHOP 0 2 4 8 P < 0. 05 PERK 2 eukaryotic initiation factor-2α eif2α 4 activating transcription factor 4 ATF4 P < 0. 05 UPR 1α inositol-requiring enzyme 1α IRE1α X 1 X-box binding protein 1 spliced XBP1s ATF6 P > 0. 05 DMAS GSK2606414 P < 0. 05 PERK P < 0. 05 caspase-3 caspase-8 caspase-9 PARP P < 0. 05 PERK-eIF2α DMAS PC9 /GR / / R734. 2 R730. 53 2015-08-11 81303114 1990-. * E-mail alexisczh@ sohu. com 檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭檭 0 1 2 3 4 2015 ESMO NED no evidence of disease 3 States National Cancer Institute of CanadaJ. J Natl Cancer Inst 2000 92 3 205-216. A 1001-1692 2016 01-0029-06 1Therasse P Arbuck SG Eisenhauer EA et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer National Cancer Institute of the United 2Suarez J. Analysis of clinical and economic implications 2 MDT of Esmo 2014 Clinical Practice Guidelines for metastatic 4 MDT colorectal cancer treatmentj. Value Health 2015 18 3 MDT 7 A446. 3Van Cutsem E Cervantes A Nordlinger B et al. Metastatic colorectal cancer ESMO Clinical Practice Guide- lines for diagnosis treatment and follow-up J. Ann On- col 2014 25 Suppl 3 iii1-9. 4. J. 2014 17 11 1060-1061.

30 Journal of Practical Oncology Vol. 31 No. 1 2016 DOI:10.13267/j.cnki.syzlzz.2016.01.008 Effect of DMAS combined with PERK inhibitor on apoptosis of human NSCLC PC9 /GR cells Yu Yu 1 Chen Zhe 2 Ruan Shanming 3 1. The First Clinical Medicine College Zhejiang Chinese Medical UniversityHangzhou 310053 China 2. Central Laboratory Zhejiang Provincial Hospital of TCM Hangzhou 310006 China 3. Department of OncologyZhejiang Provincial Hospital of TCM Hangzhou 310006 China Abstract Objective To investigate the effect of β β'-dimethylacryl shikonin DMAS combined with PKR-like ER kinase PERK inhibitor on the apoptosis of gefitinib resistant non-small-cell lung cancer NSCLC PC9 /GR cells and its molecular mechanism. Methods In DMAS treated PC9 /GR cellscell proliferation was measured by CCK-8 method and the levels of glucose regulated protein 78 GRP78 C /EBP homologous protein CHOP and proteins related to the unfolded protein response UPR signaling pathway were examined by Western blot. After treated with PERK inhibitor GSK2606414Annexin-V-PI flow cytometric analysis was used to study the cell apoptosis rate of PC9 /GR cells. The cleavage of apoptosis related proteinsincluding caspase-3caspase-8caspase-9and poly ADP-ribose polymerase PARP were analyzed by Western blot. Results DMAS inhibited the proliferation of PC9 / GR cells in a dose-dependent manner 0 5 10 15 μmol /L P < 0. 05. DMAS also dose-dependently induced PC9 /GR apoptosisas well as the cleavage of caspase-3 caspase-8 caspase-9 and PARP all P < 0. 05 endoplasmic reticulum stress markers GRP78 and CHOP were upregulated in a time-dependent manner 0 2 4 8 h P < 0. 05. Increased phosphorylation of PERK and eukaryotic initiation factor-2α eif2α were observedtogether with elevated expression of its substrate activating transcription factor 4 ATF4 all P < 0. 05. However the level of other URP related proteins were not changedincluding inositol-requiring enzyme 1α IRE1α X-box binding protein 1 spliced XBP1s and ATF6 all P > 0. 05. Compared with DMAS or GSK2606414 single treatmentdmas and GSK2606414 combined therapy led to increased cell apoptosis P < 0. 05 reduced PERK phosphorylation P < 0. 05 increased cleavage of caspase-3caspase-8caspase-9 and increased phosphorylation of PARP P < 0. 05. Conclusion PERK-eIF2α pathway plays a protective role in the pro-apoptotic process of DMAS in PC9 /GR cells. Key words carcinoma non-small-cell lung /drug therapy SHIKONIN /therapeutic use apoptosis endoplasmic reticulum stress protein kinases / -κb nuclear factor κb NF- κb non-small-cell lung cancer NSCLC 80% 8 DMAS 1 PC9 /GR DMAS PC9 /GR 2 β β'- β β'- dimethylacryl shikonin 6 4 Notch-1 7 1 1. 1 NSCLC PC9 DMAS 3 PC9 /GR DMAS 1. 2 β β'- 1 epidermal DMEM growth factor receptor EGFR 4 2 EDTA reactive oxygen species ROS 5 3 Hyclone DMAS

2016 31 1 31 PKR ER PKR-like 37 5% CO 2 10 μmol /L ER kinase PERK 2 eukaryotic initiation factor-2α eif2α P-eIF2α 4 GSK2606414 24 DMAS 10 μmol /L GSK2606414 DMAS activating transcription factor 4 ATF4 1α FACS Canto TM Ⅱ inositol-requiring enzyme 1α IRE1α X 1 X-box binding protein 1 spliced XBP1s poly ADP- PC9 /GR 25 cm 2 ribose polymerase PARP cleaved caspase-3 cleaved caspase-8 cleaved caspase-9 β-actin 0 5 10 15 μmol /L DMAS 24 Santa Cruz Biotechnology Cell Counting Kit-8 FITC Annexin V Appoptosis Detection Kit BD FACS Canto TM Ⅱ BD SDS-PAGE GSK2606414 30 10 μmol /L DMAS 4 4 10 μmol /L DMAS 10 μmol /L GSK2606414 10 μmol /L BIO-RAD DMAS 10 μmol /L GSK2606414 1. 3 PC9 PC9 /GR PC9 PC9 / Annexin V-FITC 5 μl propidium iodidepi 30 400 μl 1 Binding Buffer GR 37 5% CO 2 DMEM PBS 1 RI- 10% FBS 20 mmol /L NaHCO 3 20 mmol /L PA 30 13 300 r /min HEPES 100 U /ml 100 mg /L 80% ~ 90% 2 SDS 100 5 1. 4 CCK-8 SDS-PAGE NSCLC PC9 PC9 /GR 6 10 4 PVDF 96 37 5% CO 2 0 5 10 15 20 μmol /L Thermo VARIOSKAN FLASH 450 9 PARP 2 78 glucose nm 30 regulated protein 78 GRP78 C /EBP C /EBP homologous % = - / proteinchop PERK P-PERK eif2α P-eIF2α - 100% 3 1. 5 Annexin-V-PI PERK P-eIF2α ATF4 2 NSCLC PC9 /GR 10 10 5 ~ 15 10 5 / 12 37 5% CO 2 0 5 10 15 μmol /L DMAS 24 0. 1 ml Chemi Dox 100 μl 1 Binding Buffer 5 μl FACS Canto TM Ⅱ NSCLC PC9 /GR 1. 6 Western blot NSCLC 70% ~ 80% 1 Cell Signaling Technology P-PERK ATF6 2 10 μmol /L DMAS 0 2 4 8 3 10 μmol /L 24 15 DC 5% /BSA TBST 2 PVDF DMAS PC9 PC9 /GR 24 5% 1 4 10 μl CCK-8 1-3 cleaved caspase-3 cleaved caspase-8 cleaved caspase- ATF4 IRE1α XBP1s ATF6 3 P- 3 10 / PVDF 2 3 5 / ECL A B XRS 1. 7 SPSS 17. 0 ANOVA P < 0. 05 2 10 10 5 ~ 15 10 5 / 12 2. 1 DMAS PC9 PC9 /GR DMAS

32 Journal of Practical Oncology Vol. 31 No. 1 2016 PC9 PC9 /GR 4. 9 ± 1. 8 % 17. 6 ± DMAS 0 5 10 15 20 μmol /L 24 4. 0 % 24. 7 ± 6. 0 % 33. 0 ± 5. 0 % P < 0. 05 PC9 19. 1% 2A Western blot 26. 1% 33. 4% 53. 3% PC9 /GR caspase-3 caspase-8 caspase-9 13. 4% 28. 5% 37. 3% 57. 8% PARP P P < 0. 052B DMAS PC9 / < 0. 05 DMAS 2 GR caspase P > 0. 05 DMAS PC9 2. 3 DMAS DMAS 10 μmol /L PC9 /GR PC9 /GR 2 4 8 Western blot 1 GRP78 CHOP P < 0. 053A PERK eif2α 2 4 8 1 DMAS PC9 PC9 /GR DMAS PC9 /GR PERK- 2. 2 DMAS PC9 /GR eif2α IRE1-XBP1s ATF6 DMAS 0 5 10 15 μmol /L PC9 /GR 24 P < 0. 05 PERK eif2α P > 0. 05 PERKeIF2α ATF4 4 P < 0. 053B IRE1 α ATF6 IRE1 α XBP1s P > 0. 053C 2 DMAS PC9 /GR A B A GRP78 CHOP B PERK eif2α ATF4 PERK eif2α C IRE1α XBP1s ATF6 3 10 μmol /L DMAS PC9 /GR

2016 31 1 33 2. 4 DMAS GSK2606414 caspase-3 caspase-8 caspase-9 PARP PERK P < 0. 05 GSK2606414 10 μmol /L PERK eif2α 63. 9% DMAS ATF4 P < 0. 054A DMAS 10 μmol /L DMAS 23. 8% P < 0. 01 4B GSK2606414 DMAS PC9 / GSK2606414 P < GR DMAS 0. 05 PERK PERK-eIF2α A 10 μmol /L GSK2606414 30 10 μmol /LDMAS 4 Western blot PERK eif2α ATF4 B C 10 μmol /L DMAS 10 μmol /L GSK2606414 10 μmol /L DMAS 10 μmol /L GSK2606414 PC9 /GR 24 B Western blot caspase-3 caspase-8 caspase-9 PARP C 3 4 PERK DMAS PC9 /GR GRP78 PERK eif2a GRP78 eif2a P-eIF2a 3 ATF4 IRE1 PERK ATF6 3 DMAS PC9 /GR PERK-eIF2α PERK-eIF2α IRE1-XBP1 ATF6 unfolded protein response UPR 8 DMAS PERK-eIF2α IRE1-XBP1 ATF6 ER associated PERK protein degradation ERAD GSK2606414 DMAS PC9 /GR PERK-eIF2α DMAS PC9 /GR DMAS 9 PERK-eIF2α ROS 1 eif2a 10 2 11 12 3 PERK E2 PERK-eIF2α PERK /eif2α PERK 2 nuclear factor erythroid 2-related factor 2 IRE1-XBP1 ATF6 3 Nrf2 Kelch -1 Kelch-like

34 Journal of Practical Oncology Vol. 31 No. 1 2016 ECH-associated protein-1 Keap-1 - E2 2 - antioxidant-response elementare Keap1-Nrf2-ARE ROS DNA 13-14 pathway in vitro and in vivoj. Biochem Pharmacol 201284 4 507-512. PERK-eIF2α DMAS 8. PC9 /GR J. 2008 20 2 246-252. DMAS 9. 10Chevet EHetz CSamali Aet al. Endoplasmic reticu- 1. lum stress-activated cell reprogramming in oncogenesis NSCLC J. C. Cancer Discov2015 5 6 586-597. 2013 30 2 218-221. 2. and extrinsic activators of the unfolded protein response J. 2008 27 7 786-788. in cancer Mechanisms and targets for therapy J. Se- 3. min Cancer Biol201533 3-15. J. 2010 48 2 319-322. 4Zhao QKretschmer NBauer Ret al. Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinibj. Int J Cancer2015 137 6 1446-1456. 5Kwak SY Jeong YKKim BYet al. Beta beta-dimethylacrylshikonin sensitizes human colon cancer cells to ionizing radiation through the upregulation of reactive oxygen species J. Oncol Lett2014 7 6 1812-1818. 6Xiong YMa XYZhang Zet al. Apoptosis induced by β β-dimethylacrylshikonin is associated with Bcl-2 and NF-κB in human breast carcinoma MCF-7 cells J. Oncol Lett20136 6 1789-1793. 7Shao ZJZhang YYFan YYet al. β β-dimethylacrylshikonin exerts antitumor activity via Notch-1 signaling J. 2009 34 5 457-459. 11Tameire FVerginadis IIKoumenis C. Cell intrinsic 12Kouroku YFujita EIUeno Tet al. ER stress PERK /eif2alpha phosphorylation mediates the polyglutamine-induced LC3 conversionan essential step for autophagy formationj. Cell Death Differ2007 14 2 230-239. 13Bobrovnikova-Marjon EGrigoriadou CPytel Det al. PERK promotes cancer cell proliferation and tumor growth by limiting oxidative DNA damagej. Oncogene201029 27 3881-3895. 14Tenkerian CKrishnamoorthy JMounir Zet al. mtorc2 balances Akt activation and eif2alpha serine 51 phosphorylation to promote survival under stress. J. Mol Cancer Res201513 10 1377-1388. 檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿檿 DOI:10.13267/j.cnki.syzlzz.2016.01.024 http / /www. syzlzz. com E-mail