Research article summary (published 30 Oct 2009):

Radiosensitization effect of STI-571 on pancreatic cancer cells in vitro.

Full Abstract

PURPOSE: To examine STI-571-induced radiosensitivity in human pancreatic cancer cells in vitro. METHODS AND MATERIALS: Three human pancreatic cancer cell lines (Bxpc-3, Capan-1, and MiaPaCa-2) exhibiting different expression levels of c-Kit and platelet-derived growth factor receptor beta (PDGFRbeta) and showing different K-ras mutation types were used. For evaluation of the antitumor activity of STI-571 in combination with radiation, clonogenic survival assays, Western blot analysis, and the annexin V/propidium iodide assay with microscopic evaluation by 4',6-diamidino-2-phenylindole were conducted. RESULTS: Dramatic phosphorylated (p)-c-Kit and p-PDGFRbeta attenuation, a modest dose- and time-dependent growth inhibition, and significant radiosensitization were observed after STI-571 treatment in view of apoptosis, although the levels of growth inhibition and increased radiosensitization were different according to cell lines. The grades of radiosensitivity corresponded to the attenuation levels of p-c-Kit and p-PDGFRbeta by STI-571, particularly to those of p-c-Kit, and the radiosensitivity was partially affected by K-ras mutation in pancreatic cancer cells. Among downstream pathways associated with c-Kit or PDGFRbeta, p-PLCgamma was more closely related to radiosensitivity compared with p-Akt1 or p-extracellular signal-regulated kinase 1. CONCLUSION: STI-571 enhances radiation response in pancreatic cancer cells. This effect is affected by the attenuation levels of p-c-Kit or p-PDGFRbeta, and K-ras mutation status. Among them, p-c-Kit plays more important roles in the radiosensitivity in pancreatic cancer compared with p-PDGFRbeta or K-ras mutation status.

Author information

Author/s: Chung, Hye Won (HW); Wen, Jing (J); Lim, Jong-Baeck (JB); Bang, SeungMin (S); Park, Seung Woo (SW); Song, Si Young (SY);

Affiliation: Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-Ku, Seoul, Korea.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys), published in United States. (Language: eng)

Reference: 2009-Nov; vol 75 (issue 3) : pp 862-9

Dates: Created 2009/10/05; Completed 2009/10/20;

PMID: 19801102, status: MEDLINE (last retrieval date: 10/20/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Analysis of Variance Apoptosis Cell Line, Tumor Dose-Response Relationship, Drug Drug Screening Assays, Antitumor - methods Extracellular Signal-Regulated MAP Kinases - metabolism Formazans - metabolism Genes, ras - genetics Humans Mutation - genetics Pancreatic Neoplasms - genetics; metabolism; radiotherapy Phospholipase C gamma - metabolism

Phospholipase C gamma - metabolism Phosphorylation - drug effects Piperazines - therapeutic use Proto-Oncogene Proteins c-akt - metabolism Proto-Oncogene Proteins c-kit - metabolism Pyrimidines - therapeutic use Radiation Tolerance - drug effects; genetics Radiation-Sensitizing Agents - therapeutic use Receptor, Platelet-Derived Growth Factor beta - metabolism Tetrazolium Salts - metabolism Thiazoles - metabolism Time Factors

Associated Chemicals: Formazans (0) ; Piperazines (0) ; Pyrimidines (0) ; Radiation-Sensitizing Agents (0) ; Tetrazolium Salts (0) ; Thiazoles (0) ; imatinib (152459-95-5) ; MTT formazan (23305-68-2) ; thiazolyl blue (298-93-1) ; Proto-Oncogene Proteins c-kit (EC 2.7.1.112) ; Receptor, Platelet-Derived Growth Factor beta (EC 2.7.1.112) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.1.37) ; Proto-Oncogene Proteins c-akt (EC 2.7.1.37) ; Phospholipase C gamma (EC 3.1.4.3)

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