Cyclopamine increases the radiosensitivity of human pancreatic cancer cells by regulating the DNA repair signal pathway through an epidermal growth factor receptor-dependent pathway

Molecular Medicine Reports

Volumn 8, Issue 4, 2013, Pages 979-983

  Wu, Xiao Yang ^a   Che, Jun ^b   Sun, Ke Kang ^a   Shen, Xiao Jun ^a   Yang, Dong ^a   Zhong, Ning ^a   Zhao, Hua ^c  

^a KUNSHAN FIRST PEOPLE S HOSPITAL AFFILIATED TO JIANGSU UNIVERSITY   (China)

^b Fourth People's Hospital of Wuxi City   (China)

^c THE FIRST AFFILIATED HOSPITAL OF SOOCHOW UNIVERSITY   (China)

Author keywords

Cyclopamine; Epidermal growth factor receptor; Pancreatic cancer; Radiosensitivity

Indexed keywords

ATM PROTEIN; CELL DNA; CYCLOPAMINE; DOUBLE STRANDED DNA; EPIDERMAL GROWTH FACTOR RECEPTOR; GEFITINIB; HISTONE H2AX; HISTONE H2AX GAMMA; K RAS PROTEIN; KU ANTIGEN; UNCLASSIFIED DRUG; EGFR PROTEIN, HUMAN; H2AFX PROTEIN, HUMAN; HISTONE; QUINAZOLINE DERIVATIVE; RADIOSENSITIZING AGENT; VERATRUM ALKALOID;

APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CELL SURVIVAL; CLONOGENIC ASSAY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DNA DETERMINATION; DNA REPAIR; DOUBLE STRANDED DNA BREAK; DRUG EFFECT; FLOW CYTOMETRY; G2 PHASE CELL CYCLE CHECKPOINT; HUMAN; HUMAN CELL; IN VITRO STUDY; INTRACELLULAR SIGNALING; IONIZING RADIATION; MICRONUCLEUS; PANCREAS CANCER; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; QUANTITATIVE ANALYSIS; RADIATION EXPOSURE; RADIOSENSITIVITY; RADIOSENSITIZATION; WESTERN BLOTTING; ANTAGONISTS AND INHIBITORS; CELL CYCLE; DRUG EFFECTS; METABOLISM; PANCREAS TUMOR; PHOSPHORYLATION; PROTEIN PROCESSING; RADIATION DOSE; RADIATION RESPONSE; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

CITRUS MACROPHYLLA; ERINACEIDAE;

APOPTOSIS; CELL CYCLE; CELL LINE, TUMOR; DNA BREAKS, DOUBLE-STRANDED; DNA REPAIR; HISTONES; HUMANS; PANCREATIC NEOPLASMS; PHOSPHORYLATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; QUINAZOLINES; RADIATION TOLERANCE; RADIATION-SENSITIZING AGENTS; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION; VERATRUM ALKALOIDS;

EID: 84883426614     PISSN: 17912997     EISSN: 17913004     Source Type: Journal    
DOI: 10.3892/mmr.2013.1605     Document Type: Article

References (17)

1. Maitra A and Hruban RH: Pancreatic Cancer. Annu Rev Pathol 3: 157-188, 2008.
2. Zeng H, Yu H, Lu L, et al: Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer. Pancreas 40: 657-663, 2011.
3. Stan SD, Singh SV and Brand RE: Chemoprevention strategies for pancreatic cancer. Nat Rev Gastroenterol Hepatol 7: 347-356, 2010.
4. Mahindroo N, Punchihewa C and Fujii N: Hedgehog-Gli signaling pathway inhibitors as anticancer agents. J Med Chem 52: 3829-3845, 2009.
5. Mazumdar T, Devecchio J, Agyeman A, et al: Blocking hedgehog survival signaling at the level of the GLI genes induces DNA damage and extensive cell death in human colon carcinoma cells. Cancer Res 71: 5904-5914, 2011.
6. Feldmann G, Dhara S, Fendrich V, et al: Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res 67: 2187-2196, 2007.
7. Kumar SK, Roy I, Anchoori RK, et al: Targeted inhibition of hedgehog signaling by cyclopamine prodrugs for advanced prostate cancer. Bioorg Med Chem 16: 2764-2768, 2008.
8. Bartsch DK, Sina-Frey M, Lang S, et al: CDKN2A germline mutations in familial pancreatic cancer. Ann Surg 236: 730-737, 2002.
9. Almoguera C, Shibata D, Forrester K, et al: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53: 549-554, 1988
10. Toulany M, Kasten-Pisula U, Brammer I, et al: Blockage of epidermal growth factor receptor-phosphatidylinositol 3-kinase-AKT signaling increases radiosensitivity of K-RAS mutated human tumor cells in vitro by affecting DNA repair. Clin Cancer Res 12: 4119-4126, 2006.
11. Jiao Y, Wang HC and Fan SJ: Growth suppression and radiosensitivity increase by HMGB1 in breast cancer. Acta Pharmacol Sin 28: 1957-1967, 2007
12. Jiao Y, Ge CM, Meng QH, et al: Adenovirus-mediated expression of Tob1 sensitizes breast cancer cells to ionizing radiation. Acta Pharmacol Sin 28: 1628-1636, 2007
13. Jiao Y, Sun KK, Zhao L, et al: Suppression of human lung cancer cell proliferation and metastasis in vitro by the transducer of ErbB-2.1 (TOB1). Acta Pharmacol Sin 33: 250-260, 2012.
14. Che J, Zhang FZ, Zhao CQ, et al: Cyclopamine is a novel Hedgehog signaling inhibitor with significant anti-proliferative, anti-invasive and anti-estrogenic potency in human breast cancer cells. Oncol Lett 5: 1417-1421, 2013
15. Ahsan A, Hiniker SM, Davis MA, et al: The role of cell cycle in epidermal growth factor receptor inhibitor-mediated radiosensitization. Cancer Res 69: 5108-5114, 2009
16. Cloos CR, Daniels DH, Kalen A, et al: Mitochondrial DNA depletion induces radioresistance by suppressing G2 checkpoint activation in human pancreatic cancer cells. Radiat Res 171: 581-587, 2009
17. Kimple RJ, Vaseva AV, Cox AD, et al: Radiosensitization of EGFR/HER2 positive pancreatic cancer is mediated by inhibition of Akt independent of Ras mutational status. Clin Cancer Res 16: 912-923, 2010.